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1. Single-cell transcriptomics reveals age-resistant maintenance of cell identities, stem cell compartments and differentiation trajectories in long-lived naked mole-rats skin

Author: Aleksandra Savina, Thierry Jaffredo, Frederic Saldmann, Chris G. Faulkes, Philippe Moguelet, Christine Leroy, Delphine Del Marmol, Patrice Codogno, Lucy Foucher, Antoine Zalc, Mélanie Viltard, Gérard Friedlander, Selim Aractingi, Romain H. Fontaine, Université Paris Cité (UPCité), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Migration et différenciation des cellules souches hématopoiétiques = Migration and differentiation of hematopoietic stem cells (LBD-E06), Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire de Biologie du Développement [IBPS] (LBD), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie du Développement [IBPS] (LBD), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), School of Biological and Chemical Sciences, Queen Mary University of London (QMUL), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université de Namur [Namur] (UNamur), Centre de recherche biomédicale (CRBM), École nationale vétérinaire - Alfort (ENVA)-Université Paris-Est (UPE), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation pour la Recherche en Physiologie [Bruxelles], UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CITI Centre of Innovation in Telecommunications and Integration of services (CITI), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria), Robots coopératifs et adaptés à la présence humaine en environnements (CHROMA), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-CITI Centre of Innovation in Telecommunications and Integration of services (CITI), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Inria Lyon, and Institut National de Recherche en Informatique et en Automatique (Inria)
Subjects: skin, Aging, naked mole-rat, Mole Rats, [SDV]Life Sciences [q-bio], Longevity, Wound healing, wound healing, Stem cells, Cell Biology, Naked mole-rat, Mice, naked mole-rat skin stem cells wound healing aging, stem cells, Animals, Transcriptome, Skin
Abstract: International audience; Naked mole-rats (NMR) are subterranean rodents characterized by an unusual longevity coupled with an unexplained resistance to aging. In the present study, we performed extensive in situ analysis and single-cell RNA-sequencing comparing young and older animals. At variance with other species, NMR exhibited a striking stability of skin compartments and cell types, which remained stable over time without aging-associated changes. Remarkably, the number of stem cells was constant throughout aging. We found three classical cellular states defining a unique keratinocyte differentiation trajectory that were not altered after pseudotemporal reconstruction. Epidermal gene expression did not change with aging either. Langerhans cell clusters were conserved, and only a higher basal stem cell expression of Igfbp3 was found in aged animals. In accordance, NMR skin healing closure was similar in young and older animals. Altogether, these results indicate that NMR skin is characterized by peculiar genetic and cellular features, different from those previously demonstrated for mice and humans. The remarkable stability of the aging NMR skin transcriptome likely reflects unaltered homeostasis and resilience.
Published: 2022
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2. Yield of FDG PET/CT for Defining the Extent of Disease in Patients with Kaposi Sarcoma

Author: Louise Pesqué, Julie Delyon, Coralie Lheure, Barouyr Baroudjian, Maxime Battistella, Pascal Merlet, Céleste Lebbé, Laetitia Vercellino, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, and leboeuf, Christophe
Subjects: Cancer Research, F-18-Fluorodeoxyglucose, positron emission tomography/computed tomography, Kaposi sarcoma, disease staging, diagnostic accuracy, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; Background: Positron emission tomography/computed tomography with fluorodeoxyglucose (F-18) (FDG PET/CT) is increasingly used in Kaposi sarcoma (KS), but its value has not been assessed. Objectives: In this study, we aimed to evaluate the diagnostic accuracy of FDG PET/CT to define the extent of disease in KS. Methods: Consecutive patients with KS referred to our department for FDG PET/CT were included. The diagnostic accuracy of FDG PET/CT for cutaneous and extra-cutaneous KS staging was assessed on a per lesion basis compared to staging obtained from clinical examination, standard imaging, endoscopy, histological analyses, and follow-up. Results: From 2007 to 2017, 75 patients with FDG PET/CT were analyzed. The sensitivity and specificity of FDG PET/CT for the overall detection of KS lesions were 71 and 98%, respectively. Sensitivity and specificity were 100 and 85% for lymph nodes, 87 and 98% for bone, 87 and 100% for lungs, and 100 and 100% for muscle involvement, whereas sensitivity was only 17% to detect KS digestive involvement. The sensitivity of the diagnostic for KS cutaneous involvement increased from 73 to 88% when using a whole-body examination. Conclusion: FDG PET/CT showed good sensitivity and specificity for KS staging (digestive involvement excepted) and could be used for staging patients with active KS.
Published: 2022
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3. Patterns of ICU admissions and outcomes in patients with solid malignancies over the revolution of cancer treatment

Author: Clara Vigneron, Julien Charpentier, Sandrine Valade, Jérôme Alexandre, Samy Chelabi, Lola-Jade Palmieri, Nathalie Franck, Valérie Laurence, Jean-Paul Mira, Matthieu Jamme, Frédéric Pène, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Service de pneumologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Institut Curie [Paris], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AFSOS and Hôpital Privé de l'Ouest Parisien, and HAL UVSQ, Équipe
Subjects: [SDV] Life Sciences [q-bio], RC86-88.9, Research, [SDV]Life Sciences [q-bio], Drug-related side effects, ICU, Medical emergencies. Critical care. Intensive care. First aid, Solid tumour, Critical Care and Intensive Care Medicine, Outcome
Abstract: Background Major therapeutic advances including immunotherapy and targeted therapies have been changing the face of oncology and resulted in improved prognosis as well as in new toxic complications. The aim of this study is to appraise the trends in intensive care unit (ICU) admissions and outcomes of critically ill patients with solid malignancies. We performed a retrospective single-centre study over a 12-year period (2007–2018) including adult patients with solid malignancies requiring unplanned ICU admission. Admission patterns were classified as: (i) specific if directly related to the underlying cancer; (ii) non-specific; (iii) drug-related or procedural adverse events. Results 1525 patients were analysed. Lung and gastro-intestinal tract accounted for the two main tumour sites. The proportion of patients with metastatic diseases increased from 48.6% in 2007–2008 to 60.2% in 2017–2018 (p = 0.004). Critical conditions were increasingly related to drug- or procedure-related adverse events, from 8.8% of ICU admissions in 2007–2008 to 16% in 2017–2018 (p = 0.01). The crude severity of critical illness at ICU admission did not change over time. The ICU survival rate was 77.4%, without any significant changes over the study period. Among the 1279 patients with complete follow-up, the 1-year survival rate was 33.2%. Independent determinants of ICU mortality were metastatic disease, cancer in progression under treatment, admission for specific complications and the extent of organ failures (invasive and non-invasive ventilation, inotropes/vasopressors, renal replacement therapy and SOFA score). One-year mortality in ICU-survivors was independently associated with lung cancer, metastatic disease, cancer in progression under treatment, admission for specific complications and decision to forgo life-sustaining therapies. Conclusion Advances in the management and the prognosis of solid malignancies substantially modified the ICU admission patterns of cancer patients. Despite underlying advanced and often metastatic malignancies, encouraging short-term and long-term outcomes should help changing the dismal perception of critically ill cancer patients.
Published: 2021
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4. Teignes de l’enfant : algorithme de prise en charge après l’arrêt de la commercialisation de la griséofulvine en France

Author: Nicolas Dupin, M. Caseris, J. Toubiana, Sophie Brun, Bernard Guillot, A. Maruani, Olivier Chosidow, J. Menotti, Marie Beylot-Barry, S. Barbarot, L. Chouchana, J.-P. Gangneux, Françoise Botterel, C. Moreau, Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Tours (UT), Université de Nantes (UN), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Robert Debré, Environnement, Ville, Société (EVS), École normale supérieure de Lyon (ENS de Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Parasitologie-Mycologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hospices Civils de Lyon (HCL), HCL Groupement Hospitalier Nord [Lyon], Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-André, Université de Bordeaux (UB), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Environnement Ville Société (EVS), École normale supérieure - Lyon (ENS Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience
Published: 2021
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5. Systemic sclerosis is associated with lower limb vascular stiffness and microvascular impairment: results from a prospective study

Author: Arsène Mekinian, Jean-Benoît Monfort, Sébastien Rivière, Patricia Senet, Nathalie Baudot, Camille Francès, Vannina Seta, Charles Cassius, Annick Barbaud, Service de dermatologie et allergologie [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, medicine.medical_specialty, Duplex ultrasonography, medicine.medical_treatment, Hemodynamics, Toe-brachial index, Vascular stiffness, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Predictive Value of Tests, Internal medicine, Peripheral arterial disease, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, Prospective Studies, cardiovascular diseases, Prospective cohort study, Stroke, 030203 arthritis & rheumatology, Scleroderma, Systemic, business.industry, Microangiopathy, General Medicine, Middle Aged, medicine.disease, Connective tissue disease, 3. Good health, body regions, Amputation, Lower Extremity, Ankle-brachial index, Cardiology, Systemic sclerosis, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business
Abstract: Systemic sclerosis (SSc) is a connective tissue disease characterized by microangiopathy. Peripheral arterial disease, increasingly studied during SSc, is responsible for digital ulcers, associated with a high risk of amputation. The aim of our study was to assess the frequency of lower limb arterial impairment in SSc patients by measuring ankle-brachial index (ABI), toe pressure (TP), and toe-brachial index (TBI).Systemic sclerosis patients were included prospectively during 1 year in Tenon and Saint-Antoine Hospitals, Paris. Clinical and biological data were recorded. For each patient, ABI, TP, and TBI were measured and an arterial duplex ultrasonography was prescribed in case of abnormal results.Eighty-six patients were included (94% women, median age 62 years). Only 24% of them had no lower limb hemodynamic vascular abnormalities; 44% had an isolated microvascular abnormality (normal ABI and TBI0.75); 31% had at least a macrovascular injury associated or not with microvascular impairment (abnormal ABI) and 12.6% had a TP50 mmHg. During follow-up, there was a trend towards association of low TBI with more major adverse event (all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, and lower limb ischemic manifestations) than normal TBI.By measuring ABI and TP, we showed that 76% of SSc patients had hemodynamic arterial lower limb abnormalities related to macro- and/or microvascular impairment and that 28% had vascular stiffness. In SSc patients, ABI is not an accurate tool to detect lower limb arterial disease, likely due to underlying micro- and macrovascular changes. Key Points • The presence of lower limb macro-and/or microvascular involvement was detected in 76% of SSc patients. • In SSc patients, ABI is not an accurate tool to detect lower limb arterial disease, likely due to underlying microvascular changes and frequent arterial stiffness.
Published: 2021
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6. Deep cutaneous fungal infections in solid-organ transplant recipients

Author: L. Le Cleach, Emilie Ducroux, Sarah Guégan, Marie Thérèse Leccia, Ali Dadban, Camille Francès, Stéphane Barete, Alexandre Alanio, François Le Pelletier, Agnès Galezowski, Philippe Moguelet, Diane Lastennet, Céleste Lebbé, Julie Delyon, Service de Dermatologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de dermatologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Service de Département de santé publique [CHU Pitié-Salpêtrière], Service de Pathologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Centre Hospitalier Universitaire [Grenoble] (CHU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de dermatologie et allergologie [CHU Tenon], CHU Tenon [AP-HP], Supported by Skin and Organ Transplantation Group of the French Society of Dermatology (Groupe Peau et Greffe d'organe de la Société Française de Dermatologie)., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Cochin [AP-HP], Génétique et Génomique des Insectes Vecteurs, Département de Biostatistiques [Paris], Molecular Psychiatry Laboratory - Department of Psychiatry and Behavioural Sciences, Windeyer Institute for Medical Sciences-Royal Free and University College London Medical School, and CCSD, Accord Elsevier
Subjects: Graft Rejection, Male, Antifungal Agents, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Dermatologic Surgical Procedures, Phaeohyphomycoses, 030207 dermatology & venereal diseases, 0302 clinical medicine, Prevalence, MESH: Immunocompromised Host, Skin, MESH: Dermatomycoses, solid-organ transplant recipients, MESH: Aged, MESH: Middle Aged, Immunosuppression, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], deep cutaneous fungal infection, Phaeohyphomycosis, antifungal treatment, MESH: Young Adult, 030220 oncology & carcinogenesis, Female, MESH: Immunosuppressive Agents, Immunosuppressive Agents, Adult, MESH: Phaeohyphomycosis, medicine.medical_specialty, Adolescent, MESH: Transplant Recipients, Hyphae, MESH: Graft Rejection, MESH: Organ Transplantation, Dermatology, Immunocompromised Host, Young Adult, 03 medical and health sciences, MESH: Skin, MESH: Hyphae, Internal medicine, medicine, Dermatomycoses, Humans, phaeohyphomycosis, MESH: Prevalence, Aged, Retrospective Studies, MESH: Adolescent, MESH: Dermatologic Surgical Procedures, MESH: Humans, business.industry, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, Organ Transplantation, medicine.disease, MESH: Antifungal Agents, Transplant Recipients, MESH: Male, Calcineurin, Observational study, Histopathology, Solid organ transplantation, business, MESH: Female
Abstract: Background Deep cutaneous fungal infections (DCFIs) are varied in immunosuppressed patients, with few data for such infections in solid-organ transplant recipients (s-OTRs). Objective To determine DCFI diagnostic characteristics and outcome with treatments in s-OTRs. Methods A 20-year retrospective observational study in France was conducted in 8 primary dermatology-dedicated centers for s-OTRs diagnosed with DCFIs. Relevant clinical data on transplants, fungal species, treatments, and outcomes were analyzed. Results Overall, 46 s-OTRs developed DCFIs (median delay, 13 months after transplant) with predominant phaeohyphomycoses (46%). Distribution of nodular lesions on limbs and granulomatous findings on histopathology were helpful diagnostic clues. Treatments received were systemic antifungal therapies (48%), systemic antifungal therapies combined with surgery (28%), surgery alone (15%), and modulation of immunosuppression (61%), leading to complete response in 63% of s-OTRs. Limitations Due to the retrospective observational design of the study. Conclusions Phaeohyphomycoses are the most common DCFIs in s-OTRs. Multidisciplinary teams are helpful for optimal diagnosis and management.
Published: 2020
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7. HAVCR2 mutations are associated with severe hemophagocytic syndrome in subcutaneous panniculitis-like T-cell lymphoma

Author: Sonigo, Gabrielle, Battistella, Maxime, Beylot-Barry, Marie, Ingen-Housz-Oro, Saskia, Franck, Nathalie, Barète, Stéphane, Boulinguez, Serge, Dereure, Olivier, Bonnet, Nathalie, Brice, Pauline, Boccara, Olivia, Bodemer, Christine, Adamski, Henri, D'Incan, Michel, Ortonne, Nicolas, Fraitag, Sylvie, Brunet-Possenti, Florence, Dalle, Stéphane, Suarez, Felipe, Skowron, François, Haidar, Dima, Maubec, Eve, Bohelay, Gerome, Laroche, Liliane, Mahé, Antoine, Birckel, Elodie, Bouaziz, Jean-David, Brocheriou, Isabelle, Dubois, Romain, Faiz, Sarah, Fadlallah, Jehane, Ram-Wolff, Caroline, Carlotti, Agnès, Bens, Guido, Balme, Brigitte, Vergier, Béatrice, Laurent-Roussel, Sara, Deschamps, Lydia, Carpentier, Olivier, Moguelet, Philippe, Herve, Genevieve, Comoz, Francois, Le Gall, François, Leverger, Guy, Finon, Antoine, Augereau, Olivier, Blechet, Claire, Kerdraon, Rémy, Lamant, Laurence, Tournier, Emilie, Franck, Frédéric, Costes-Martineau, Valérie, Szablewski, Vanessa, Taix, Sebastien, Beschet, Isabelle, Guérin, Frédéric, Sepulveda Garrido, Fernando, Bagot, Martine, De Saint Basile, Geneviève, Michonneau, David, de Masson, Adèle, Socié, Gérard, Bodemer, Shristine ChB, Marçais, Ambroise, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], CHU Henri Mondor, Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Toulouse [Toulouse], Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Hôpital Nord [CHU - APHM], Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Pontchaillou [Rennes], CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'immuno-hématologie pédiatrique [CHU Necker], Centre Hospitalier de Valence (CH DE VALENCE), Centre hospitalier de Valence, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Avicenne [AP-HP], Hôpital pasteur [Colmar], Service de Dermatologie [AP-HP Hôpital Saint-Louis], Service d'Anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière] (ACP), Mouvement, Équilibre, Performance, Santé (MEPS), Université de Pau et des Pays de l'Adour (UPPA), Service de Dermatologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiopathologie du cancer du foie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Service de pathologie [CHU Bichat], Service d’Anatomie et cytologie pathologiques [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Service d'anatomie et cytologie pathologiques [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Laboratoire d'aérologie (LAERO), Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Unité d'hématologie et de transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service d’anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomie et cytologie pathologiques [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Centre Hospitalier Régional d'Orléans (CHR), Laboratoire d'aérologie (LA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Immunologie humaine, physiopathologie & immunithérapie (HIPI (UMR_S_976 / U976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Anatomie et cytologie pathologiques [CHU Tenon], CHU Tenon [AP-HP], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), COLO, Mouniati, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Pathology, medicine.medical_specialty, Panniculitis, [SDV]Life Sciences [q-bio], Immunology, 2 supplemental tables, [SDV.CAN]Life Sciences [q-bio]/Cancer, Lymphoma, T-Cell, HAVCR2, Biochemistry, Lymphohistiocytosis, Hemophagocytic, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Subcutaneous Panniculitis-Like T-Cell Lymphoma, 9 references Article type: Letter Scientific category: Lymphoma, Humans, Medicine, Genetic Predisposition to Disease, Hepatitis A Virus Cellular Receptor 2, Genetic Association Studies, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Hemophagocytic lymphohistiocytosis, business.industry, Cell Biology, Hematology, medicine.disease, 3. Good health, Lymphoma, [SDV] Life Sciences [q-bio], 1 supplemental figure, 030220 oncology & carcinogenesis, Mutation, Mutation (genetic algorithm), 2 tables, Female, business, Biomarkers
Abstract: International audience
Published: 2020
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8. Shifting the Balance of Activating and Inhibitory Natural Killer Receptor Ligands on BRAFV600E Melanoma Lines with Vemurafenib

Author: Eric Pasmant, Brigitte Dréno, Houssem Benlalam, Marina Colombo, Antoine Toubert, Emmanuelle Fourmentraux-Neves, Frédéric Vély, Florence Faure, Fanny Bouquet, Ariel Savina, Marie-Françoise Avril, Sylvie Rusakiewicz, Laurence Zitvogel, Meriem Messaoudene, Anne Caignard, Alexandra Frazao, Eric Vivier, Alloimmunité-Autoimmunité-Transplantation (A2T), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Immunologie [AP-HM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut ROCHE [Boulogne-Billancourt], Roche S.A.S, Service de biochimie et de génétique moléculaire [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie [CHU Cochin], This work was supported by Roche Pharmaceuticals, Fondation ARC, Institut National du Cancer (2011-PLBIO-06, for M. Colombo and E. Fourmentraux-Neves, and PAIR Melanoma 2013-066), Ligue Nationale Contre le Cancer (for M. Messaoudene), and Cancerop^ole Ile de France (for A. Frazao)., Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Alloimmunité-Autoimmunité-Transplantation ( A2T ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ), Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], and Bernardo, Elizabeth
Subjects: 0301 basic medicine, MAPK/ERK pathway, Cancer Research, NK Cell Lectin-Like Receptor Subfamily K, Melanoma, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Natural killer T cell, NKG2D, medicine.disease, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 3. Good health, 03 medical and health sciences, 030104 developmental biology, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cancer research, medicine, Receptor, Vemurafenib, neoplasms, V600E, medicine.drug
Abstract: Over 60% of human melanoma tumors bear a mutation in the BRAF gene. The most frequent mutation is a substitution at codon 600 (V600E), leading to a constitutively active BRAF and overactivation of the MAPK pathway. Patients harboring mutated BRAF respond to kinase inhibitors such as vemurafenib. However, these responses are transient, and relapses are frequent. Melanoma cells are efficiently lysed by activated natural killer (NK) cells. Melanoma cells express several stress-induced ligands that are recognized by activating NK-cell receptors. We have investigated the effect of vemurafenib on the immunogenicity of seven BRAF-mutated melanoma cells to NK cells and on their growth and sensitivity to NK-cell–mediated lysis. We showed that vemurafenib treatment modulated expression of ligands for two activating NK receptors, increasing expression of B7-H6, a ligand for NKp30, and decreasing expression of MICA and ULBP2, ligands for NKG2D. Vemurafenib also increased expression of HLA class I and HLA-E molecules, likely leading to higher engagement of inhibitory receptors (KIRs and NKG2A, respectively), and decreased lysis of vemurafenib-treated melanoma cell lines by cytokine-activated NK cells. Finally, we showed that whereas batimastat (a broad-spectrum matrix metalloprotease inhibitor) increased cell surface ULBP2 by reducing its shedding, vemurafenib lowered soluble ULBP2, indicating that BRAF signal inhibition diminished expression of both cell-surface and soluble forms of NKG2D ligands. Vemurafenib, inhibiting BRAF signaling, shifted the balance of activatory and inhibitory NK ligands on melanoma cells and displayed immunoregulatory effects on NK-cell functional activities. Cancer Immunol Res; 5(7); 582–93. ©2017 AACR.
Published: 2017
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9. Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility

Author: Eduardo Nagore, Caroline Hayward, Christopher I. Amos, Douglas F. Easton, Zaida García-Casado, Julie Lang, Anjali K. Henders, Veronica Höiom, Lisa Bowdler, Kathryn P. Burdon, Laura Del Regno, Nick Orr, Per Arne Andresen, Tongwu Zhang, Rose Yang, Myriam Brossard, Eric K. Moses, Dirk Schadendorf, Laura Cattaneo, Casey Rowe, Essen-Heidelberg Investigators, Hans-Joachim Schulze, Jamie E Craig, D. Timothy Bishop, Anne E. Cust, Johan Hansson, David E. Elder, Nelleke A. Gruis, Donato Calista, Wei V. Chen, Abrar A. Qureshi, Amy Hutchinson, Pilar Galan, Leanne Wallace, Jennifer H. Barrett, Nilesh J. Samani, Maria Teresa Landi, Per Helsing, Andreas Hadjisavvas, Fengju Song, Celia Requena, Elizabeth M. Gillanders, Arantxa Rodriguez, Joan Anton Puig-Butille, Blair H. Smith, Mark Smithers, Michael Malasky, Marianna Sanna, Miriam Potrony, Maria A. Loizidou, Evangelos Evangelou, Richard A. Scolyer, Karen A. Pooley, Rachel E. Neale, Mario Falchi, Adèle C. Green, Monica Rodolfo, Ketty Peris, Licia Rivoltini, Mark M. Iles, Catherine M. Olsen, Alexander J. Stratigos, Tadeusz Dębniak, Weiyin Zhou, H. Peter Soyer, Xin Li, Margaret A. Tucker, Rajesh Kumar, Håkan Olsson, Anders Molven, Nicholas G. Martin, Anthony J. Swerdlow, Aurelie Vogt, Lars A. Akslen, Stuart MacGregor, Sarah V. Ward, Hamida Mohamdi, Bruna Dalmasso, Grant W. Montgomery, Rona M. MacKie, Esther Azizi, Gonçalo R. Abecasis, Chiara Menin, Alison M. Dunning, Ibd investigators, Kevin M. Brown, Jiali Han, Veryan Codd, Graham J. Mann, Nicholas K. Hayward, Marko Hočevar, Eitan Friedman, Richard A. Sturm, Paola Queirolo, Qtwin Investigators, Lawrie Wheeler, Lars G. Fritsche, Shenying Fang, Kiarash Khosrotehrani, Nicole A Kukutsch, Pol Gimenez-Xavier, Belynda Hicks, Matthew Zawistowski, Alessia Visconti, Jessica Harris, Chad M. Brummett, Paola Ghiorzo, andMe, David G. Hunter, Veronique Bataille, Julia Newton-Bishop, Srdjan Novaković, Amfs Investigators, Siranoush Manoukian, Jianxin Shi, Mitchell J. Machiela, G. Mark Lathrop, Josep Malvehy, Katerina P. Kypreou, Susana Puig, Dale R. Nyholt, I. Stefanaki, Maria Concetta Fargnoli, Lisa A. Simms, Kerrie McAloney, M. Malt, Adam J. Trower, Matthew Law, Lei Song, Paul D.P. Pharoah, Christian Ingvar, Jiyeon Choi, Alisa M. Goldstein, Jeffrey E. Lee, Mark Harland, Cristina Pellegrini, Daniela Massi, Sarah Simi, Scott D. Gordon, Jacobo Martinez, Florence Demenais, Kristine Jones, Graham L. Radford-Smith, David C. Whiteman, Lorenza Pastorino, Lisa Elefanti, Arcangela De Nicolo, Mario Mandalà, Juliette Randerson-Moor, Q-Mega, Jan Lubinski, Stephen J. Chanock, Marie-Françoise Avril, David L. Duffy, Helen Gogas, Nienke van der Stoep, Peter A. Kanetsky, Georgina V. Long, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), University of Leeds, QIMR Berghofer Medical Research Institute, National and Kapodistrian University of Athens (NKUA), Ospedale Policlinico San Martino [Genoa], Universita degli studi di Genova, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Maurizio Bufalini Hospital, University of L'Aquila [Italy] (UNIVAQ), Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), Cyprus Institute of Neurology and Genetics, University of Athens Medical School [Athens], The University of Sydney, Universitat de Barcelona (UB), Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy], University of Michigan [Ann Arbor], University of Michigan System, Instituto Valenciano de Oncologia, Veneto Institute of Oncology IOV-IRCCS [Padua, Italy], IRCCS Istituto Nazionale dei Tumori [Milano], Ninewells Hospital and Medical School [Dundee], Cyprus Institute (CyI), Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University of Queensland [Brisbane], Haukeland University Hospital, University of Bergen (UiB), Geisel School of Medicine at Dartmouth, Oslo University Hospital [Oslo], Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], King‘s College London, Menzies School of Health Research [Australia], Charles Darwin University, The University of Texas M.D. Anderson Cancer Center [Houston], University of Leicester, Flinders University [Adelaide, Australia], West Pomeranian University of Technology Szczecin, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), National Human Genome Research Institute (NHGRI), Leiden University Medical Center (LUMC), Karolinska Institutet [Stockholm], Queensland University of Technology [Brisbane] (QUT), Institute of Oncology Ljubljana, Harvard T.H. Chan School of Public Health, Lund University [Lund], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Glasgow, Statistical Genetics, and Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH) United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USAU19CA148112SEARCH team (Cancer Research UK) C490/A16561AOCS (US Army Medical Research and Material Command) DAMD17-01-1-0729Canadian Institutes of Health Research (CIHR)Cancer Council Victoria Queensland Cancer Fund Cancer Council New South Wales Cancer Council South Australia Cancer Council Western Australia Cancer Council Tasmania National Health and Medical Research Council of AustraliaID400413ID400281National Health and Medical Research Council of Australia National Health and Medical Research Council of Australia National Health and Medical Research Council of Australia National Health and Medical Research Council of Australia Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS Ministry of Health, Italy Associazione Italiana per la Ricerca sul Cancro (AIRC)IG 15460Spanish Fondo de Investigaciones Sanitarias grant - FEDER 'Una manera de hacer Europa' PI15/00716PI15/00956CIBER de Enfermedades Raras of the Instituto de Salud Carlos III, Spain - European Development Regional Fund 'A way to achieve Europe' ERDF AGAUR of the Catalan Government, Spain 2014_SGR_603European CommissionEuropean Commission Joint Research CentreLSHC-CT-2006-018702European Union (EU) 'Fundacio La Marato de TV3', Catalonia, Spain 201331-30'Fundacion Cientifica de la Asociacion Espanola Contra el Cancer', Spain GCB15152978SOENCERCA Programme/Generalitat de Catalunya Italian Ministry of the University and Scientific Research (PRIN-2012 grant) 2012JJX494Melanoma Research Alliance United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI)CA88363CA83115CA122838CA87969CA055075CA100264CA133996CA49449National Health and Medical Research Council of Australia200071241944339462380385389927389875389891389892389938443036442915442981496610496675496739552485552498APP1049894Cancer Council Queensland Cancer Institute New South Wales Australian GovernmentDepartment of Industry, Innovation and ScienceCooperative Research Centres (CRC) Programme Australian Cancer Research Foundation Wellcome TrustWT084766/Z/08/ZNational Health and Medical Research Council of Australia Australian Research Council Department of Health and Human Services (DHHS)
Subjects: Sequence Variants, Male, medicine.medical_specialty, Skin Neoplasms, Genotype, Medizin, Identifies 3, Genome-wide association study, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Malignant-melanoma, 0302 clinical medicine, Genetics, medicine, Genetic predisposition, Nevus, Humans, Hla Class-i, Genetic Predisposition to Disease, Polymorphism, Melanoma, 030304 developmental biology, Telomere Length, Cancer, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Loci, Pigmentation, E-cadherin, Single Nucleotide, medicine.disease, Genetic architecture, Attributable Fraction, 3. Good health, Phenotype, Female, Genetic Loci, Genome-Wide Association Study, Cutaneous melanoma, Medical genetics, Settore MED/35 - MALATTIE CUTANEE E VENEREE, 030217 neurology & neurosurgery, Familial Melanoma
Abstract: Meta-analysis of 36,760 cases and 375,188 controls identifies 54 loci associated with susceptibility to cutaneous melanoma. Further analysis combining nevus count and hair color GWAS results provide insights into the genetic architecture of melanoma.Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 x 10(-8)) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis.
Published: 2020
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10. Sickle cell disease induces resistance to cutaneous carcinogenesis

Author: Selim Aractingi, François Lionnet, Boutros Soutou, Anoosha Habibi, Patricia Senet, Université Saint-Joseph de Beyrouth (USJ), Service de dermatologie et allergologie [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, medicine.medical_specialty, Carcinogenesis, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Anemia, Sickle Cell, Disease, medicine.disease_cause, Gastroenterology, Malignant transformation, Young Adult, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Humans, Medicine, Skin cancer, Hydroxyurea, Pharmacology (medical), Genetics (clinical), business.industry, Research, Sickle cell disease, Leg Ulcer, lcsh:R, Actinic keratosis, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, Skin ulcer, medicine.disease, 3. Good health, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, Skin Carcinoma, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: Background While skin carcinomas are reported in chronic ulcers and in patients treated with hydroxyurea (HU) for myeloproliferative neoplasms, no skin carcinoma has been reported in patients with sickle cell disease (SCD), presenting chronic skin ulcers or treated with HU. The objective was to estimate the risk of cutaneous malignant transformation in SCD patients with prolonged leg ulcers or under HU therapy. Results In this cross-sectional study, the cohort consisted of 1543 patients. In the first series, 29 patients presented a total of 53 ulcers lasting more than two years. The median age was 35 ± 8.4 years old. The median duration for a single ulcer was 9.2 ± 7 years. None of the examined ulcers showed any suspicious area of malignant transformation. In the second series, 187 patients treated with HU for more than two years were identified. The median age was 31.3 ± 9.9 years old. The median duration of treatment with HU was 6 ± 3.2 years. No skin carcinoma or actinic keratosis was recorded. Conclusions This study showed that skin carcinogenesis did not occur in our series of SCD patients exposed to transforming events such as long term HU treatment or prolonged leg ulcers.
Published: 2020
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11. Epidemiological changes in cutaneous lymphomas: an analysis of 8593 patients from the French Cutaneous Lymphoma Registry

Author: Nicolas Franck, E. Maubec, Gaëlle Quéreux, Caroline Ram-Wolff, Philippe Courville, Laurence Lamant, Olivier Dereure, G. Dobos, Isabelle Templier, Florent Grange, Saskia Ingen-Housz-Oro, Jacques Rouanet, Martine Bagot, N. Josselin, O. Augereau, Stéphane Barete, Serge Boulinguez, Isabelle Moulonguet, Marisa Battistella, Nicolas Ortonne, Anne Durlach, A. Carlotti, Pascal Joly, S. Taix, Sophie Dalac, Michel D'Incan, F. Franck, Laurent Mortier, A. de Masson, Marie Beylot-Barry, Charlée Nardin, Jacqueline Rivet, M.-D. Vignon-Pennamen, Laurence Michel, Liliane Laroche, Anne Pham-Ledard, Romain Dubois, T. Petrella, Béatrice Vergier, Florent Amatore, Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Hôpital Cochin [AP-HP], Centre hospitalier de Cahors, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Dermatologie (CHU de Dijon), Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Département de Pathologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Claude Huriez [Lille], CHU Lille, Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de dermatologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, CHU Grenoble, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Cahors, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC)
Subjects: medicine.medical_specialty, Mycosis fungoides, Heterogeneous group, business.industry, Incidence (epidemiology), [SDV]Life Sciences [q-bio], CBCL, Retrospective cohort study, Dermatology, medicine.disease, Cutaneous lymphoma, 3. Good health, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Male patient, Epidemiology, medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: Background Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. Objectives The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. Methods Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. Results The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. Conclusions Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.
Published: 2020
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12. VIH et autres IST sur le grill

Author: N. Dupin, Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 030203 arthritis & rheumatology, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, [SDV]Life Sciences [q-bio], Dermatology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019
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13. Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens

Author: Linda Grillová, Jan Oppelt, Lenka Mikalová, Markéta Nováková, Lorenzo Giacani, Anežka Niesnerová, Angel A. Noda, Ariel E. Mechaly, Petra Pospíšilová, Darina Čejková, Philippe A. Grange, Nicolas Dupin, Radim Strnadel, Marcus Chen, Ian Denham, Natasha Arora, Mathieu Picardeau, Christopher Weston, R. Allyn Forsyth, David Šmajs, Biologie des Spirochètes / Biology of Spirochetes, Institut Pasteur [Paris], Masaryk University [Brno] (MUNI), Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Departments of Medicine and Global Health, University of Washington [Seattle], Instituto de Medicina Tropical Pedro Kouri, Cristallographie (Plateforme) - Crystallography (Platform), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Veterinary Research Institute [Brno] (VRI), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Masaryk University and University Hospital Brno, University Hospital Brno, Monash University [Melbourne], Melbourne Sexual Health Centre [Australia], Alfred Health, Universität Zürich [Zürich] = University of Zurich (UZH), GeneticPrime Dx, Department of Biology [San Diego], San Diego State University (SDSU), This research was supported by funds from the Faculty of Medicine, Masaryk University to junior researchers (LGr, MN, and PP), the Grant Agency of the Czechia (GA17-25455S) and by the Ministry of Health of the Czechia (17-31333A) to DŠ. Core Facility Bioinformatics of CEITEC Masaryk University is gratefully acknowledged for the obtaining of the scientific data presented in this manuscript. Computational resources were provided by the CESNET LM2015042 and the CERIT Scientific Cloud LM2015085, provided under the program 'Projects of Large Research, Development, and Innovations Infrastructures'., University of Zurich, Šmajs, David, Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Department of Biology [San Diego State Univ] (Biology SDSU), and MURGUET, SYLVIE
Subjects: Microbiology (medical), [SDV]Life Sciences [q-bio], Population, lcsh:QR1-502, syphilis, 340 Law, 610 Medicine & health, direct whole genome sequencing, Genome, Genetic recombination, Microbiology, 2726 Microbiology (medical), lcsh:Microbiology, 03 medical and health sciences, 510 Mathematics, Treponema pallidum subsp. pallidum, medicine, Genetic variability, education, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Gene, Original Research, 030304 developmental biology, Genetics, 0303 health sciences, education.field_of_study, Genetic diversity, Treponema, biology, 030306 microbiology, culture-independent bacterial enrichment, 2404 Microbiology, Treponema pallidum subsp pallidum, medicine.disease, biology.organism_classification, 10218 Institute of Legal Medicine, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, recombination- driven diversity, Syphilis, recombination-driven diversity
Abstract: We would like to thank Prof. Nicholas Robert Thomson (Wellcome Sanger Institute) for his valuable insights during the preparation of the manuscript. We also thank Robert Anthony Gaultney for his assistance with the English revision of the manuscript.; International audience; Syphilis, caused by Treponema pallidum subsp. pallidum (TPA), remains an important public health problem with an increasing worldwide prevalence. Despite recent advances in in vitro cultivation, genetic variability of this pathogen during infection is poorly understood. Here, we present contemporary and geographically diverse complete treponemal genome sequences isolated directly from patients using a methyl-directed enrichment prior to sequencing. This approach reveals that approximately 50% of the genetic diversity found in TPA is driven by inter- and/or intra-strain recombination events, particularly in strains belonging to one of the defined genetic groups of syphilis treponemes: Nichols-like strains. Recombinant loci were found to encode putative outer-membrane proteins and the recombination variability was almost exclusively found in regions predicted to be at the host-pathogen interface. Genetic recombination has been considered to be a rare event in treponemes, yet our study unexpectedly showed that it occurs at a significant level and may have important impacts in the biology of this pathogen, especially as these events occur primarily in the outer membrane proteins. This study reveals the existence of strains with different repertoires of surface-exposed antigens circulating in the current human population, which should be taken into account during syphilis vaccine development.
Published: 2019
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14. S100-EPISPOT: A New Tool to Detect Viable Circulating Melanoma Cells

Author: Aurélie De Roeck, Françoise Garima, Jean-Pierre Daurès, Laurent Meunier, Laure Cayrefourcq, Françoise Perriard, Pierre-Emmanuel Stoebner, C. Garcia, F. Fichel, Catherine Alix-Panabières, Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de l'Environnement Industriel et des Risques (INERIS), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Oncology, Treatment response, medicine.medical_specialty, Population, CellSearch®, [SDV.CAN]Life Sciences [q-bio]/Cancer, circulating tumor cells, S100 protein, Article, 03 medical and health sciences, 0302 clinical medicine, Circulating tumor cell, Internal medicine, Biomarkers, Tumor, melanoma, Humans, Medicine, EPISPOT, In patient, Liquid biopsy, education, lcsh:QH301-705.5, Aged, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, education.field_of_study, liquid biopsy, business.industry, Melanoma, S100 Proteins, General Medicine, Middle Aged, Neoplastic Cells, Circulating, medicine.disease, 3. Good health, Molecular Diagnostic Techniques, lcsh:Biology (General), Homogeneous, 030220 oncology & carcinogenesis, Female, business, Software
Abstract: Metastatic melanoma is one of the most aggressive and drug-resistant cancers with very poor overall survival. Circulating melanoma cells (CMCs) were first described in 1991. However, there is no general consensus on the clinical utility of CMC detection, largely due to conflicting results linked to the use of heterogeneous patient populations and different detection methods. Here, we developed a new EPithelial ImmunoSPOT (EPISPOT) assay to detect viable CMCs based on their secretion of the S100 protein (S100-EPISPOT). Then, we compared the results obtained with the S100-EPISPOT assay and the CellSearch&reg, CMC kit using blood samples from a homogeneous population of patients with metastatic melanoma. We found that S100-EPISPOT sensitivity was significantly higher than that of CellSearch&reg, Specifically, the percentage of patients with &ge, 2 CMCs was significantly higher using S100-EPISPOT than CellSearch&reg, (48% and 21%, respectively, p = 0.0114). Concerning CMC prognostic value, only the CellSearch&reg, results showed a significant association with overall survival (p = 0.006). However, due to the higher sensitivity of the new S100-EPISPOT assay, it would be interesting to determine whether this functional test could be used in patients with non-metastatic melanoma for the early detection of tumor relapse and for monitoring the treatment response.
Published: 2019
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15. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial

Author: Hang-Phuong Pham, Philippe Seksik, Beatrice Banneville, Olivier Chazouillères, Fabien Pitoiset, Julien Champey, Bruno Fautrel, David Saadoun, Laurent Beaugerie, Valérie Doppler, Patrice Cacoub, Karim El Soufi, Selim Aractingi, Christophe Corpechot, Roberta Lorenzon, David Klatzmann, Michelle Rosenzwajg, Francis Berenbaum, Claude C.A. Bernard, Eric Vicaut, Jérémie Mariau, Elodie Regnier, Joe-Elie Salem, Anne Daguenel-Nguyen, Jérémie Sellam, Arsène Mekinian, Claire Ribet, Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service de Gastroentérologie et nutrition [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Service de rhumatologie [CHU Saint-Antoine], Service d'hépatologie [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], Service de médecine interne [CHU Saint-Antoine], Immunologie - Immunopathologie - Immunothérapeutique (I3), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Service de Pharmacie [CHU Saint Antoine], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Gestionnaire, Hal Sorbonne Université, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Immunologie antivirale systémique et cérébrale, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Thérapie des maladies du muscle strié, Unité de Recherche Clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), ANR-16-RHUS-0001,iMAP,iMAP(2016), Bernard, Claude, Service de biothérapies [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Etude et de Recherche sur le Matériau Bois (LERMAB), Université de Lorraine (UL), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service d'hépatologie [Saint-Antoine], Service de Médecine Interne [CHU Saint-Antoine], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CIC Paris Est, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Adult, Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Immunology, Autoimmune hepatitis, medicine.disease_cause, T-Lymphocytes, Regulatory, General Biochemistry, Genetics and Molecular Biology, Autoimmunity, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Psoriasis, medicine, Immunology and Allergy, Humans, Immunologic Factors, Prospective Studies, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, Ankylosing spondylitis, business.industry, Middle Aged, medicine.disease, Ulcerative colitis, 3. Good health, Clinical trial, [SDV] Life Sciences [q-bio], 030104 developmental biology, Treatment Outcome, Rheumatoid arthritis, Interleukin-2, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, Granulomatosis with polyangiitis
Abstract: ObjectiveRegulatory T cells (Tregs) prevent autoimmunity and control inflammation. Consequently, any autoimmune or inflammatory disease reveals a Treg insufficiency. As low-dose interleukin-2 (ld-IL2) expands and activates Tregs, it has a broad therapeutic potential.AimWe aimed to assess this potential and select diseases for further clinical development by cross-investigating the effects of ld-IL2 in a single clinical trial treating patients with 1 of 11 autoimmune diseases.MethodsWe performed a prospective, open-label, phase I–IIa study in 46 patients with a mild to moderate form of either rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Behcet’s disease, granulomatosis with polyangiitis, Takayasu’s disease, Crohn’s disease, ulcerative colitis, autoimmune hepatitis and sclerosing cholangitis. They all received ld-IL2 (1 million IU/day) for 5 days, followed by fortnightly injections for 6 months. Patients were evaluated by deep immunomonitoring and clinical evaluation.Resultsld-IL2 was well tolerated whatever the disease and the concomitant treatments. Thorough supervised and unsupervised immunomonitoring demonstrated specific Treg expansion and activation in all patients, without effector T cell activation. Indication of potential clinical efficacy was observed.ConclusionThe dose of IL-2 and treatment scheme used selectively activate and expand Tregs and are safe across different diseases and concomitant treatments. This and preliminary indications of clinical efficacy should licence the launch of phase II efficacy trial of ld-IL2 in various autoimmune and inflammatory diseases.Trial registration numberNCT01988506.
Published: 2018
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16. Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer

Author: Olivier Benveniste, Dimitri Psimaras, Karine Auré, Tali-Anne Szwebel, Nicolas Weiss, Sarah Leonard-Louis, Baptiste Hervier, Jean-Frédéric Bruch, Werner Stenzel, Yves Allenbach, Timothée Lenglet, Nora Kramkimel, Pauline Laly, Samuel Knauss, Thierry Maisonobe, Mehdi Touat, Omar Ben Hadj Salem, Claire Lethrosne, Jacques Cadranel, Anthony Behin, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Università degli Studi di Pavia = University of Pavia (UNIPV), Sorbonne Université - Faculté de Médecine (SU FM), Fondation Ophtalmologique Adolphe de Rothschild [Paris], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Foch [Suresnes], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Groupe de recherche clinique Biomarqueurs Théranostiques des Cancers Bronchiques Non à Petites Cellules (GRC 4 - Theranoscan), CHU Tenon [AP-HP], Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
Subjects: myalgia, Male, Durvalumab, [SDV]Life Sciences [q-bio], Pembrolizumab, Gastroenterology, 0302 clinical medicine, Neoplasms, Medicine, Receptors, Cholinergic, Creatine Kinase, Myositis, Aged, 80 and over, education.field_of_study, Middle Aged, Magnetic Resonance Imaging, Europe, Myocarditis, 030220 oncology & carcinogenesis, Cytokines, Female, medicine.symptom, Nivolumab, Programmed cell death 1 ligand 2, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Ipilimumab, 03 medical and health sciences, Young Adult, Internal medicine, Humans, education, Muscle, Skeletal, Aged, Autoantibodies, Retrospective Studies, business.industry, Electromyography, Myocardium, Receptor Protein-Tyrosine Kinases, medicine.disease, Neurology (clinical), business, Apoptosis Regulatory Proteins, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: ObjectiveTo report the clinicopathologic features and outcome of myositis in patients treated with immune checkpoint inhibitors (ICIs) (irMyositis).MethodsWe retrospectively analyzed patients diagnosed with irMyositis in tertiary centers in Paris, France, and Berlin, Germany, from January 2015 to July 2017. The main outcomes were clinical manifestations and muscle histology, which included major histocompatibility complex class I (MHC-I), C5b-9, CD3, CD4, CD8, CD20, CD68, programmed cell death protein 1 (PD-1), programmed cell death 1 ligand 1 (PD-L) 1, and programmed cell death 1 ligand 2 (PD-L2).ResultsTen patients with metastatic cancer were included; median age was 73 (range 56–87) years. Median follow-up duration was 48 (range 16–88) weeks. Six patients developed myositis during nivolumab therapy, 1 patient during pembrolizumab, 1 patient during durvalumab, and 2 patients during combined nivolumab and ipilimumab. Median delay between ICI initiation and myositis onset was 25 (range 5–87) days. Clinical manifestations were dominated by acute or subacute myalgia (8 patients) and limb-girdle (7), axial (7), and oculomotor (7) weakness. Four patients had evidence of myocarditis. In all patients, creatine kinase levels were elevated (median 2,668, range 1,059–16,620 U/L), while anti-acetylcholine receptor and myositis-associated antibodies were negative. Electrodiagnostic studies showed myopathic process without decrement in all patients. Muscle biopsy constantly showed multifocal necrotic myofibers, sarcolemmal MHC-I, and endomysial inflammation, consisting mainly of CD68+ cells expressing PD-L1 and CD8+ cells expressing PD-1. ICI treatment was withdrawn in all patients; 9 patients received immunosuppressive therapy, which consistently led to marked clinical improvement.ConclusionsirMyositis presents with remarkably homogeneous and unique clinicopathologic features, expanding the nosologic spectrum of inflammatory myopathies in patients with cancer. ICI withdrawal and treatment with corticosteroids improve outcome.
Published: 2018
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17. Extra-haematological manifestations related to human parvovirus B19 infection: retrospective study in 25 adults

Author: Gilles Blaison, Laurent Chiche, Luc Mouthon, Alban Deroux, Marion Dollat, Emmanuelle Dernis, Nicolas Dupin, Luc de Saint-Martin, Benjamin Chaigne, Olivier Lambotte, Benjamin Terrier, François Lifermann, Grégoire Cormier, Emilie Berthoux, Jérémie Sellam, Nathalie Costedoat-Chalumeau, Thomas Sené, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Service de Médecine Interne [Dax], Centre Hospitalier de Dax, Centre Hospitalier Universitaire [Grenoble] (CHU), Centre hospitalier Saint Joseph - Saint Luc [Lyon], Le Mans Université (UM), Hôpital Foch [Suresnes], Centre Hospitalier Louis Pasteur [Dole], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Saint-Antoine [AP-HP], Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier Départemental Vendée, Service de rhumatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]
Subjects: Adult, Male, Vasculitis, medicine.medical_specialty, Peripheral neuropathy, Pleural effusion, Arthritis, lcsh:Infectious and parasitic diseases, Intravenous immunoglobulin, lupus, Arthritis, Rheumatoid, Parvoviridae Infections, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Focal segmental glomerulosclerosis, Glomerulonephritis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pregnancy, Internal medicine, Membranoproliferative glomerulonephritis, medicine, Parvovirus B19, Human, Humans, lcsh:RC109-216, 030212 general & internal medicine, Prospective Studies, Pregnancy Complications, Infectious, Intravenous immunoglobulin lupus, Aged, Retrospective Studies, 030203 arthritis & rheumatology, Aged, 80 and over, Hemophagocytic lymphohistiocytosis, business.industry, Mononeuritis Multiplex, Immunoglobulins, Intravenous, Middle Aged, medicine.disease, 3. Good health, Infectious Diseases, Female, business, Human parvovirus B19, Myopericarditis, Research Article
Abstract: International audience; Background: describe extra-haematological manifestations associated with human parvovirus B19 (HPV-B19) infection.Methods: we conducted a nationwide multicentre study to retrospectively describe the characteristics and outcome of extra-haematological manifestations in French adults.Results: data from 25 patients followed from 2001 to 2016 were analysed. Median age was 37.9 years (range: 22.7–83.4), with a female predominance (sex ratio: 4/1). Only 3 patients had an underlying predisposing condition (hemoglobinopathy or pregnancy). The most common manifestations were joint (80%) and skin (60%) involvement. Four patients (16%) had renal involvement (endocapillary proliferative or membranoproliferative glomerulonephritis, focal segmental glomerulosclerosis). Three patients (12%) had peripheral nervous system involvement (mononeuritis, mononeuritis multiplex, Guillain-Barré syndrome) and 2 (8%) presented muscle involvement. Other manifestations included hemophagocytic lymphohistiocytosis (n = 1), myopericarditis and pleural effusion (n = 1) and lymphadenopathy and splenomegaly mimicking lymphoma with spleen infarcts (n = 1). Immunological abnormalities were frequent (56.5%). At 6 months, all patients were alive and 54.2% were in complete remission. In 2 patients, joint involvement evolved into rheumatoid arthritis. Six patients (24%) received intravenous immunoglobulin (IVIg), with a good response in the 3 patients with peripheral nervous system involvement.Conclusions: HPV-B19 infection should be considered in a wide range of clinical manifestations. Although the prognosis is good, IVIg therapy should be discussed in patients with peripheral nerve involvement. However, its efficacy should be further investigated in prospective studies.
Published: 2018
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18. Efficacy of Immunotherapy in Patients with Metastatic Mucosal or Uveal Melanoma

Author: Mona Amini-Adle, Pierre Marcant, Yannick Le Corre, Caroline Dutriaux, Nora Kramkimel, Anne Bénédicte Duval Modeste, N. Litrowski, C. Lesage, Nicolas Meyer, Amir Khammari, Caroline Gaudy-Marqueste, C. Mignard, Aurélie Deschamps Huvier, Eve Maubec, Thierry Lesimple, Laurent Mortier, Florence Brunet-Possenti, L. Visseaux, Géraldine Jeudy, A. Stefan, Marie-Françoise Avril, Sabiha Trabelsi, Henri Montaudié, François Aubin, Pascal Joly, Laurent Machet, André Gillibert, Marie-Thérèse Leccia, Jean-Philippe Arnault, Nathalie Beneton, E. Wierzbicka-Hainaut, Dan Lipsker, Service de dermatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Bordeaux [Bordeaux], Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Hôpital Claude Huriez [Lille], CHU Lille, Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Département de dermatologie, CHU Marseille, CHU Marseille, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Département de dermatologie, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département de la santé publique [CHU Strasbourg], CHU Strasbourg, Centre Hospitalier Le Mans (CH Le Mans), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de dermatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Dermatologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Dermatology Department, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Département Pluridisciplinaire de Médecine, Dermatologie, CHU Grenoble-Hôpital Michallon, Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-André, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris Descartes - Paris 5 (UPD5), Hôpital de la Timone [CHU - APHM] (TIMONE), Université Francois Rabelais [Tours], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire [Grenoble] (CHU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hôpital Avicenne [AP-HP], Université Paris 13 (UP13), PRES Université Nantes Angers Le Mans (UNAM), Université de Strasbourg (UNISTRA), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Groupe Hospitalier du Havre Hôpital Jacques Monod (MONTIVILLIERS) (GHH), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), and TAN, Yossan-Var
Subjects: 0301 basic medicine, medicine.medical_specialty, Article Subject, medicine.medical_treatment, Gastroenterology, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Stage (cooking), Chemotherapy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Melanoma, Mucosal melanoma, Retrospective cohort study, Immunotherapy, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Research Article
Abstract: Background: The objective was to assess the response rate and survival of patients with metastatic mucosal melanoma (MM) and uveal melanoma (UM) treated with anti-CTLA-4 or anti-PD-1 monoclonal antibodies (mAbs).Methods: A multicenter retrospective study was performed in 25 dermatology departments in France. All patients with stage III-C to IV MM or UM who were treated with anti-CTLA-4 or anti-PD-1 mAbs between 2008 and 2016 were included and compared after adjustment for main prognostic factors with a second cohort of patients treated with chemotherapy. Tumor response was evaluated according to RECIST v. 1.1 criteria at Week 12.Results: Four-hundred-and-thirty-nine patients were included, 229 MM (151 immunotherapy, 78 chemotherapy) and 210 UM (100 immunotherapy, 110 chemotherapy). Response rates of MM patients treated with immunotherapy were 18/151 (11.9%; 95% CI:7.2%-18.2%), versus 11/78 (14.1%, 95% CI:7.3%-23.8%) in patients treated with chemotherapy (p=0.87). No tumor response was observed in UM patients treated with immunotherapy, versus 4/110 responses (3.6%, 95% CI:1.0-9.0%) in patients treated with chemotherapy (p=0.15). The adjusted overall survival (OS) of MM patients treated with immunotherapy was longer than that of patients treated with chemotherapy HR=0.62 (95% CI: 0.43-0.91), p=0.014, with an unadjusted median OS of 15.97 months [interquartile range (IQR)=6.89-27.11] and 8.82 months [IQR=5.02-14.92], respectively. The adjusted OS of UM patients treated with immunotherapy was not significantly different from that of patients treated with chemotherapy (HR=0.98, 95% CI: 0.66-1.44) p=0.92, with an unadjusted median OS of 13.38 months [IQR=6.03-29.57] and 11.02 months [IQR=6.13-23.93], respectively.Conclusion: Immunotherapy significantly improves OS for MM. The prognosis of metastatic UM remains poor., Immunotherapy significantly improves OS for MM. The prognosis of metastatic UM remains poor.
Published: 2018
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19. Clinical and pathological significance of cutaneous manifestations in ANCA-associated vasculitides

Author: Claire Le Jeunne, Selim Aractingi, Benoit Terris, François Maurier, Guillaume Le Guenno, Luc Mouthon, Agnès Carlotti, Alice Bérezné, Jonathan London, Alexiane Dallot, Nicolas Froment, Olivier Aumaître, Benjamin Terrier, Laurent Antunes, L. Frumholtz, Sara Laurent-Roussel, Nicolas Dupin, Loïc Guillevin, Sylvie Fraitag, Jean Louis Kemeny, Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Service de médecine interne, Hôpital Sainte-Blandine-Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), CHU Clermont-Ferrand, Service de Pathologie, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie [Aulnay-sous-Bois], Hôpital Robert Ballanger [Aulnay-sous-Bois], Service d'Anatomie Pathologique [CHU Clermont-Ferrand], Service de pathologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anatomie et de cytologie pathologiques [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Service de Dermatologie [CHU Cochin], VELUX, Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de médecine interne, hôpital Gabriel-Montpied, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Centre Hospitalier Universitaire Estaing, CHU Estaing, CHU Cochin [AP-HP], Centre Hospitalier Universitaire Gabriel Montpied, Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], CHU Pitié-Salpêtrière [APHP]-Université Pierre et Marie Curie - Paris 6 (UPMC), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Livedo, Pathology, medicine.medical_specialty, Immunology, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Xanthoma, Skin Diseases, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Recurrence, Edema, medicine, Humans, Immunology and Allergy, Clinical significance, Pathological, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, business.industry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Prognosis, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Purpura, Phenotype, medicine.symptom, business, Vasculitis, Pyoderma gangrenosum
Abstract: Objectives Cutaneous manifestations (CM) in ANCA-associated vasculitides (AAV) are frequent, but data on clinical significance and clinical-pathological correlations are lacking. Methods We conducted a multicenter, retrospective study including 1553 AAV patients. Clinical, biological and pathological features have been analyzed, and tissue samples from 46 biopsies were reviewed in a blind manner. Results CM were more frequent in EGPA (53.0%) and MPA (51.9%) than in GPA (36.7%). Lesions more frequently associated with GPA were oral ulcers (4.6% vs. 2.5% in EGPA and 0.3% in MPA), while pyoderma gangrenosum and palpebral xanthoma were specific to GPA. Lesions associated with MPA were segmentary edema (19.5% vs. 12.7% in EGPA and 4.3% in GPA) and livedo (12.4% vs. 0.5% and 2.6%, respectively), whereas those associated with EGPA were urticarial lesions (11.5% vs. 1.9% in GPA and 3.5% in MPA) and nodules (12,2% vs. 8.9% in GPA and 4.7% in MPA). In GPA, CM patients had more frequent vasculitis than granulomatous phenotype, and poorer relapse-free and overall survival. Pathological analysis showed vasculitis and/or granulomatous infiltrates in 87.5% of GPA, in 61.1% of EGPA and in all MPA. Vasculitis was more frequently observed in purpura and nodules, while granulomas were differently located and organized within vessels or interstitium according to the type of lesions. Conclusion Each AAV seemed to be associated with a peculiar pattern of cutaneous lesions. CM are associated with poorer prognosis in GPA. Clinical-pathological correlations showed no specific feature of each AAV, whereas granulomatous infiltrates differ according to the type of lesions.
Published: 2017
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20. Circulating Tumor DNA Measurement by Picoliter Droplet-Based Digital PCR and Vemurafenib Plasma Concentrations in Patients with Advanced BRAF-Mutated Melanoma

Author: Alicja Puszkiel, Pierre Laurent-Puig, Jean-Louis Golmard, Audrey Thomas-Schoemann, Fanny Garlan, Nora Kramkimel, Gaëlle Noé, Valérie Taly, Michel Vidal, Nicolas Dupin, Benoit Blanchet, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe labellisée Ligue contre le Cancer, Université Sorbonne Paris Cité (USPC), Centre Universitaires des Saints-Pères, Unité Fonctionnelle de Pharmacocinétique et Pharmacochimie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe de Pharmacologie Clinique Oncologique [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Synthèse et structure de molécules d'interet pharmacologique (SSMIP), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), This work was supported by theMinistère de l’Enseignement Supérieur et de la Recherche, the Université Paris-Descartes, the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé et de la Recherche Médicale (INSERM), the Agence Nationale de la Recherche (ANR Nanobiotechnologies, no. ANR-10-NANO-0002-09), the SIRIC CARPEM and the ligue nationale contre le cancer (LNCC, Program BEquipe labellisée LIGUE', no. EL2016.LNCC/VaT). FG thanks the Fondation Servier for a fellowship within the Frontiers in Life Science PhD program (FdV)., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and TALY, Valerie
Subjects: Male, 0301 basic medicine, Cancer Research, Indoles, [SDV]Life Sciences [q-bio], Polymerase Chain Reaction, 0302 clinical medicine, Pharmacology (medical), Digital polymerase chain reaction, Neoplasm Metastasis, Vemurafenib, Melanoma, Sulfonamides, Middle Aged, Prognosis, 3. Good health, [SDV] Life Sciences [q-bio], Oncology, Circulating tumor DNA, 030220 oncology & carcinogenesis, Plasma concentration, Female, medicine.drug, Adult, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, In patient, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Inverse correlation, neoplasms, Survival analysis, Aged, Neoplasm Staging, business.industry, DNA, medicine.disease, Survival Analysis, 030104 developmental biology, Endocrinology, Mutation, Cancer research, business, Follow-Up Studies
Abstract: International audience; BACKGROUND:Circulating tumor DNA (ctDNA) has been reported as a prognostic marker in melanoma. In BRAF V600-mutant melanoma, a plasma under-exposure to vemurafenib could favor emerging resistance but no biological data are available to support this hypothesis.OBJECTIVE:We aimed to investigate the relationship between vemurafenib plasma concentrations and the ctDNA plasma concentration during follow-up of BRAF-mutated melanoma patients.PATIENTS AND METHODS:Eleven patients treated with single-agent vemurafenib for advanced BRAF V600-mutant melanoma were analyzed in an exploratory monocentric study. The vemurafenib plasma concentration was measured by liquid chromatography. ctDNA was extracted from plasma samples and the ctDNA concentration was evaluated using picoliter droplet-based digital PCR with Taqman® detection probes targeting the BRAF p.V600E/K mutation and wild-type BRAF sequences.RESULTS:At baseline, plasma ctDNA was detectable in 72% (n = 8/11) of patients and the ctDNA concentration decreased in 88% of these patients (n = 7/8) from day (D) 0 to D15 after vemurafenib initiation. During follow-up, an increased ctDNA concentration was detected in nine patients: in five patients, the first increase in ctDNA concentrations followed a decrease in vemurafenib concentrations. More interestingly, an inverse correlation between vemurafenib concentration and ctDNA concentrations was demonstrated (p = 0.026). The ctDNA concentration at baseline was associated with overall survival (hazard ratio = 2.61, 95% CI 1.04-6.56; p = 0.04).CONCLUSIONS:This study demonstrates the relevance of vemurafenib plasma monitoring during the follow-up of metastatic melanoma patients. Plasma drug monitoring and ctDNA concentrations could be combined to monitor tumor evolution in melanoma patients treated with anti-BRAF therapies.
Published: 2017
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21. STAT3 Mediates Nilotinib Response in KIT-Altered Melanoma: A Phase II Multicenter Trial of the French Skin Cancer Network

Author: Zakia Idir, Elif Hindié, Marie-Françoise Avril, Sandrine Mansard, Anne Pham-Ledard, Bernard Guillot, Philippe Saiag, Céleste Lebbé, Sylvie Chevret, Nicolas Meyer, Stéphane Dalle, Julie Delyon, D. Legoupil, Jean-François Deleuze, Florent Grange, Samia Mourah, Nicolas Dumaz, Christophe Bedane, Maxime Battistella, Guido Bens, Thomas Jouary, Jean-Philippe Arnault, Victor Renault, Laurent Machet, Sophie Dalac, Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), CIC - Biotherapie - Saint Louis ((CIC-BT 301)), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistiques et information médicale [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CH Pau, Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Recherche en Cancérologie de Lyon (CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Centre Hospitalier Régional d'Orléans (CHR), Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Clermont-Ferrand, Département de Dermatologie [CHU de Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire épidémiologie et oncogénèse des tumeurs digestives, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Département de la Recherche Clinique et du Développement, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Fondation Jean Dausset CEPH, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de médecine nucléaire [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Université de Bordeaux (UB), Cancer et Transplantation : Physiopathologie et Réponse Thérapeutique (UMR 1165), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], Hôpital Saint-Louis, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: 0301 basic medicine, Male, STAT3 Transcription Factor, Skin Neoplasms, Administration, Oral, Antineoplastic Agents, Dermatology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Multicenter trial, Cell Line, Tumor, medicine, Clinical endpoint, Humans, Phosphorylation, STAT3, Molecular Biology, Melanoma, Aged, Cell Proliferation, biology, business.industry, Cell Biology, Exons, Middle Aged, medicine.disease, 3. Good health, Proto-Oncogene Proteins c-kit, 030104 developmental biology, Pyrimidines, Treatment Outcome, Nilotinib, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Mutation, biology.protein, STAT protein, Cancer research, Female, Skin cancer, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug, Signal Transduction
Abstract: International audience; Mutated oncogenic KIT is a therapeutic target in melanoma. We conducted a multicenter phase II trial on the KIT inhibitor nilotinib in patients with unresectable melanoma harboring KIT alteration. The primary endpoint was the response rate (complete response or partial response following Response Evaluation Criteria in Solid Tumors criteria) at 6 months. Pharmacodynamic studies using KIT sequencing, qPCR array, and immunostaining of downstream KIT effectors were performed during treatment. Twenty-five patients were included and received 400 mg oral nilotinib twice daily. At 6 months, nilotinib induced tumor response in four patients. The best overall response rate was 20% and the disease control rate was 56%, limited to patients harboring exon 11 or 13 mutations. Four patients exhibited durable response, including three persisting (3.6 and 2.8 years for two patients with stage IIIC and 2.5 years for one with IVM1b melanoma). A reduction in signal transducer and activator of transcription (STAT) 3 phosphorylation and its effectors (BCL-2, MCL-1) in tumors during follow-up was significantly associated with clinical response. In the KIT-mutated melanoma cell line M230, nilotinib reduced STAT3 signaling and STAT inhibitors were as efficient as KIT inhibitors in reducing cell proliferation. Our study evidences a significant association between STAT3 inhibition and response to nilotinib, and provides a rationale for future research assessing STAT inhibitors in KIT-mutated melanoma.
Published: 2017
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22. Subcutaneous Panniculitis-like T-cell Lymphoma: Immunosuppressive Drugs Induce Better Response than Polychemotherapy

Author: Christine Bodemer, Saskia Ingen-Housz-Oro, Tony Petrella, Olivier Hermine, Nathalie Franck, Sylvie Fraitag, Martine Bagot, David Michonneau, Maxime Battistella, Marie Beylot-Barry, Béatrice Vergier, Stéphane Barete, Nicole Brousse, Nicolas Ortonne, Marc Maynadié, Laboratoire d'anatomie pathologique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maisonneuve-Rosemont Hospital Research Center, University of Montreal, CHU Henri Mondor [Créteil], Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anatomie pathologique [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Dpt anatomie pathologique [CHU Bordeaux], Université de Bourgogne (UB), Service de dermatologie [CHU Necker], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [Saint-Louis], Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique Adulte [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Dpt Dermatologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de Bourgogne ( UB ), Service de dermatologie [CHU Necker-Enfants malades], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Oncodermatologie, immunologie et cellules souches cutanées ( DIO U976 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Panniculitis, Time Factors, Biopsy, medicine.medical_treatment, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 030207 dermatology & venereal diseases, 0302 clinical medicine, Subcutaneous Panniculitis-Like T-Cell Lymphoma, Antineoplastic Combined Chemotherapy Protocols, Child, medicine.diagnostic_test, Remission Induction, General Medicine, Middle Aged, 3. Good health, Treatment Outcome, Immunosuppressive drug, Child, Preschool, 030220 oncology & carcinogenesis, Disease Progression, Female, France, Immunosuppressive Agents, Adult, medicine.medical_specialty, Adolescent, [ SDV.IMM.IMM ] Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Lymphoma, T-Cell, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Medical history, Pathological, Proportional Hazards Models, Retrospective Studies, business.industry, Autoantibody, Infant, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Lymphoma, business, [ SDV.MHEP.DERM ] Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare condition usually considered to have a favourable prognosis. However, it is not known whether polychemotherapy or immunosuppressive-based therapy is the best approach for treating SPTCL. Using data collected between 2000 and 2012 in France, we analysed clinical, biological and pathological data of 27 patients with SPTCL. Medical history revealed that 40% of patients had been previously diagnosed with an autoimmune disorder and 22% with inflammatory panniculitis. Haemophagocytic syndrome was present in 37% of cases. Autoantibodies were positive in 65% of cases. Complete remission (CR) was reached in 74% of cases. Immunosuppressive drug treatment was given in 69.5% of patients (group 1) and polychemotherapy in 30.5% (group 2). CR was 81.2% and 28.5% (p?=?0.025), respectively. Progression rate was 6.2% and 42.8% (p?=?0.067), respectively. This study suggests that immunosuppressive drugs should be considered as the first-line treatment for SPTCL.
Published: 2017
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23. Re-epithelialization of pathological cutaneous wounds is improved by local mineralocorticoid receptor antagonism

Author: Ludovic Waeckel, Frederic Jaisser, Van Tuan Nguyen, Dorinne Desposito, Selim Aractingi, Eve Maubec, Nicolette Farman, Dany Nassar, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dpt of Basic Science, Thai Nguyen University of Agriculture and Forestry, Service de dermatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Université Paris Diderot - Paris 7 ( UPD7 ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]
Subjects: 0301 basic medicine, Keratinocytes, medicine.medical_specialty, Mineralocorticoid receptor, Wound healing, Human skin, Dermatology, Pharmacology, Administration, Cutaneous, Biochemistry, Amiloride, Ointments, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Glucocorticoid receptor, Glucocorticoid, Internal medicine, medicine, Animals, Humans, Receptor, Molecular Biology, Glucocorticoids, Mineralocorticoid Receptor Antagonists, Skin, Clobetasol, Epidermis (botany), integumentary system, business.industry, Cell Biology, 3. Good health, Blockade, 030104 developmental biology, Endocrinology, Receptors, Mineralocorticoid, chemistry, Spironolactone, Epidermis, business, [ SDV.MHEP.DERM ] Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.drug, Re-epithelialization
Abstract: Impaired cutaneous wound healing is a social burden. It occurs as a consequence of glucocorticoid treatment in several pathologies. Glucocorticoids (GC) bind not only to the glucocorticoid receptor but also to the mineralocorticoid receptor (MR), both expressed by keratinocytes. In addition to its beneficial effects through the glucocorticoid receptor, GC exposure may lead to inappropriate MR occupancy. We hypothesized that dermatological use of MR antagonists (MRA) might be beneficial by overcoming the negative impact of GC treatment on pathological wounds. The potent GC clobetasol, applied as an ointment to mouse skin, or added to cultured human skin explants, induced delayed wound closure and outgrowth of epidermis with reduced proliferation of keratinocytes. Delayed wound re-epithelialization was rescued by local MRA application. Normal skin was unaffected by MRA. The benefit of MR blockade is explained by the increased expression of MR in clobetasol-treated mouse skin. Blockade of the epithelial sodium channel by phenamil also rescued cultured human skin explants from GC-impaired growth of the epidermis. MRA application over post-biopsy wounds of clobetasol-treated skin zones of healthy volunteers (from the Interest of Topical Spironolactone's Administration to Prevent Corticoid-induced Epidermal Atrophy clinical trial) also accelerated wound closure. In conclusion, we propose repositioning MRA for cutaneous application to improve delayed wound closure occurring in pathology.
Published: 2016
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24. Paradoxical simultaneous regression and progression of lesions in a phase II study of everolimus in classic Kaposi sarcoma

Author: Céleste Lebbé, F. Morinet, V. Furlan, Félix Agbalika, Nicolas Dupin, Bernard Guillot, Thomas Jouary, Samia Mourah, Maxime Battistella, H.M. Teisserenc, Raphaël Porcher, Delphine Kerob, Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'épidémiologie Clinique [Hôtel-Dieu], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, Cancer et Transplantation : Physiopathologie et Réponse Thérapeutique (UMR 1165), Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de microbiologie [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre des Innovations Thérapeutiques en Oncologie et Hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Laboratoire Jean Dausset d'Immunologie et d'Histocompatibilité [AP-HP Hôpital Saint-Louis], Alloimmunité-Autoimmunité-Transplantation (A2T), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Oncology, 0303 health sciences, medicine.medical_specialty, Everolimus, Classic Kaposi Sarcoma, business.industry, Phases of clinical research, Dermatology, Virology, Regression, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Medicine, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030304 developmental biology, medicine.drug
Abstract: International audience
Published: 2015
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25. Inflammatory bowel disease after allogeneic stem cell transplantation

Author: O Georges, I Boussen, Marie-Thérèse Rubio, Mohamad Mohty, Selim Aractingi, Harry Sokol, Nadia Hoyeau-Idrissi, J P Hugot, Service de rhumatologie, inflammation-immunopathologie- biothérapie [CHU Saint-Antoine] (DHU i2B ), CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Origine, structure et évolution de la biodiversité, Centre National de la Recherche Scientifique (CNRS), ALWP-EBMT & Département d'hématologie et de thérapie cellulaire [AP-HP Hôpital Saint-Antoine], AP-HP - Hôpital Saint-Antoine, Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Origine, structure et évolution de la biodiversité (OSEB), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de rhumatologie, inflammation-immunopathologie- biothérapie [CHU Saint-Antoine] ( DHU i2B ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université Paris Descartes - Paris 5 ( UPD5 ), Mammifères et Oiseaux - MNHN ( UMR5202 ), and Muséum National d'Histoire Naturelle ( MNHN )
Subjects: Transplantation, Pathology, medicine.medical_specialty, business.industry, Hematology, 030230 surgery, medicine.disease, Inflammatory bowel disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Graft-versus-host disease, Text mining, Immunology, medicine, 030211 gastroenterology & hepatology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Progenitor cell, Stem cell, business, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; no abstract
Published: 2015
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26. Increase lymphangiogenesis in melanoma during pregnancy: correlation with the prolactin signalling pathway

Author: Rodero, Mathieu P, Prignon, A., Avril, M.F., Boitier, F., Aractingi, S., Khosrotehrani, K., Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and University of Queensland [Brisbane]
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2013
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27. Phenotypic and Functional Characteristics of Blood Natural Killer Cells from Melanoma Patients at Different Clinical Stages

Author: Giulia Fregni, Eduardo Marinho, Johan Chanal, Anne Caignard, Emmanuelle Fourmentraux-Neves, Meriem Messaoudene, Sarra Mazouz-Dorval, Eve Maubec, Marie-Françoise Avril, Isabelle Cremer, Isabelle Scheer-Senyarich, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de dermatologie, Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), HAL UPMC, Gestionnaire, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)
Subjects: Cytotoxicity, Immunologic, Male, Skin Neoplasms, lcsh:Medicine, Lymphocyte Activation, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Cell Degranulation, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Interleukin 21, 0302 clinical medicine, Immunophenotyping, Cytotoxic T cell, lcsh:Science, Melanoma, Cells, Cultured, Aged, 80 and over, 0303 health sciences, Multidisciplinary, Middle Aged, Flow Cytometry, Immunohistochemistry, 3. Good health, Killer Cells, Natural, NK Cell Lectin-Like Receptor Subfamily K, 030220 oncology & carcinogenesis, Interleukin 12, Female, Research Article, Adult, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Young Adult, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, medicine, Humans, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Aged, Neoplasm Staging, 030304 developmental biology, [ SDV.IMM.II ] Life Sciences [q-bio]/Immunology/Innate immunity, Lymphokine-activated killer cell, Natural Cytotoxicity Triggering Receptor 1, lcsh:R, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, NKG2D, medicine.disease, Coculture Techniques, Immunology, Interleukin-2, lcsh:Q, [ SDV.MHEP.DERM ] Life Sciences [q-bio]/Human health and pathology/Dermatology, K562 Cells, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; Melanomas are aggressive skin tumors characterized by high metastatic potential. Immunotherapy is a valuable alternative for metastatic melanoma patients resistant to chemotherapy. Natural Killer (NK) cells are efficient anti-tumor cytotoxic effectors. We previously showed that blood NK cells from stage IV metastatic melanoma patients display decreased NK receptors and that chemotherapy modifies the functional status of blood NK cells. To investigate the role of NK cells along melanoma progression, we have here studied NK cells from patients at different stages of the disease. First, we showed that ex vivo NK cells from certain stage III–IV patients displayed low degranulation potential. Using a dynamic label-free assay, we found that immunoselected IL-2 activated blood NK cells from patients efficiently lysed melanoma cells through NKp46 and NKG2D receptors, independently to the clinical stage. Moreover, the ex vivo phenotype of circulating NK cells from 33 patients (stage I to IV) was extensively analyzed. NK cells from patients displayed higher variability in the percentages of Natural Cytotoxicity Receptors (NCR) and Natural Killer Group 2D (NKG2D) receptor expression compared to donor NK cells. The main defect was the decreased expression of NCR1 (NKp46) by NK cells from metastatic patients. Interestingly, we found a positive correlation between the NK cell percentages of NKp46 and the duration of stage IV in melanoma patients. Finally, we showed that NK cells infiltrated primary melanomas and displayed a predominant peritumoral distribution. These results are new arguments for the development of NK-based therapies in melanoma patients.
Published: 2013
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28. A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma

Author: Bertolotto-Ballotti, Corine, Lesueur, Fabienne, Giuliano, Sandy, Strub, Thomas, de Lichy, Mahaut, Bille, Karine, Dessen, Philippe, d'Hayer, Benoit, Mohamdi, Hamida, Remenieras, Audrey, Maubec, Eve, de La Fouchardière, Arnaud, Molinié, Vincent, Vabres, Pierre, Dalle, Stéphane, Poulalhon, Nicolas, Martin-Denavit, Tanguy, Thomas, Luc, Andry-Benzaquen, Pascale, Dupin, Nicolas, Boitier, Françoise, Rossi, Annick, Perrot, Jean-Luc, Labeille, Bruno, Robert, Caroline, Escudier, Bernard, Caron, Olivier, Brugières, Laurence, Saule, Simon, Gardie, Betty, Gad, Sophie, Richard, Stéphane, Couturier, Jérôme, Teh, Bin Tean, Ghiorzo, Paola, Pastorino, Lorenza, Puig, Susana, Badenas, Celia, Olsson, Hakan, Ingvar, Christian, Rouleau, Etienne, Lidereau, Rosette, Bahadoran, Philippe, Vielh, Philippe, Corda, Eve, Blanché, Hélène, Zelenika, Diana, Galan, Pilar, Renseigné, Non, Aubin, François, Bachollet, Bertrand, Becuwe, Céline, Berthet, Pascaline, Bignon, yves Jean, Bonadona, Valérie, Bonafe, Jean-Louis, Bonnet-Dupeyron, Marie-Noëlle, Cambazard, Fréderic, Chevrant-Breton, Jacqueline, Coupier, Isabelle, Dalac, Sophie, Demange, Liliane, d'Incan, Michel, Dugast, Catherine, Faivre, Laurence, Vincent-Fétita, Lynda, Gauthier-Villars, Marion, Gilbert, Brigitte, Grange, Florent, Grob, Jean-Jacques, Humbert, Philippe, Janin, Nicolas, Joly, Pascal, Kerob, Delphine, Lasset, Christine, Leroux, Dominique, Levang, Julien, Limacher, Jean-Marc, Livideanu, Cristina, Longy, Michel, Lortholary, Alain, Stoppa-Lyonnet, Dominique, Mansard, Sandrine, Mansuy, Ludovic, Marrou, Karine, Matéus, Christine, Maugard, Christine, Meyer, Nicolas, Nogues, Catherine, Souteyrand, Pierre, Venat-Bouvet, Laurence, Zattara, Hélène, Chaudru, Valérie, Lenoir, Gilbert M, Lathrop, Mark, Davidson, Irwin, Avril, Marie-Françoise, Demenais, Florence, Ballotti, Robert, Bressac-de Paillerets, Brigitte, Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes, Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), AxesSim, Plateforme de Bioinformatique [Gustave Roussy], Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de dermatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomopathologie [Fort de France, Martinique], CHU Fort de France, Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Bases Moleculaires de l'Homeostasie Cutanee : Inflammation, Reparation et Cancer, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie, Centre Hospitalier Sud, Hospices Civils, Lyon, Parallel Cooperative Multi-criteria Optimization (DOLPHIN), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille (CRIStAL) - UMR 9189 (CRIStAL), Ecole Centrale de Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Ecole Centrale de Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Valorisation Recherche et Innovations Alimentaire (Valorial), University Hospital of St-Etienne, Department of Dermatology, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'immunothérapie, Institut Gustave Roussy (IGR), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Signalisation normale et pathologique de l'embryon aux thérapies innovante des cancers, Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cytokines et Immunologie des Tumeurs Humaines (U753), Laboratoire de Génétique Oncologique [Villejuif], École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Oncologique EPHE, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, Service de Génétique Oncologique, Institut Curie, Van Andel Research Institute, Grand Rapids, Michigan, Van Andel Institute [Grand Rapids], University of Barcelona, Hospital Clinic Barcelona, Lund University [Lund], Department of Surgery, Clinical Sciences, Genetique Moleculaire des Cancers d'Origine Epitheliale, Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de recherche européen pour la polyarthrite rhumatoïde (GenHotel - EA 3886), Université d'Évry-Val-d'Essonne (UEVE), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Cochin [AP-HP], Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre méditérannéen de médecine moléculaire (C3M), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématopoïèse normale et pathologique, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Section Génétique - Groupe Prédispositions génétiques au cancer, Centre International de Recherche contre le Cancer (CIRC), Apoptose, cancer et immunité (U848), Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'anatomie pathologique, Hôpital Saint Joseph, Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Consultation de génétique, Département de Pédiatrie, Service de Pathologie, Institut Curie [Paris], Department of Oncology, Clinical Sciences, Department of Cancer Epidemiology, Clinical Sciences, Department of Surgery, University Hospital of Lund, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Hôpital René HUGUENIN (Saint-Cloud), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de génétique Epidémiologique, Centre Léon Bérard [Lyon], CHU Saint-Etienne, Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Polyclinique de Courlancy, Service de Dermatologie, Hôtel-Dieu, CRLCC Eugène Marquis (CRLCC), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Service de Genetique medicale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM), Département de Génétique, CHU, Liège, Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Dermatology, Service d'onco-hématologie et génétique, CHU Grenoble, Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de diagnostic génétique, Hôpital Universitaire de Strasbourg, Strasbourg, Laboratoire de biostatistique, CHU Strasbourg, Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Département de Génétique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Functional Genomics and Cancer, Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université Paris Diderot - Paris 7 (UPD7), We thank the patients and family members who participated in this study and the clinicians who identified these families, the French Familial Melanoma Study Group and the Inherited Predisposition to Kidney Cancer network. We acknowledge the contribution of the IGR Biobank for providing MELARISK samples and the CEPH Biobank for processing DNA samples. We thank L. Larue, J, Feunteun, A. Sarasin and E. Solary for critical reviews of the manuscript. We thank V. Lazar and S. Forget for coordination of the IGR's genomics and genetic platforms, N. Pata-Merci, V. Marty, S. Le Gras and A. Chabrier for their technical expertise, and M. Barrois for technical counselling. We also thank A. Boland for DNA extraction and quality control for genome-wide genotyping. This work was supported by grants from INSERM, Ligue Nationale Contre Le Cancer (PRE05/FD and PRE 09/FD) to F. D., Programme Hospitalier de Recherche Clinique (PHRC 2007/AOM-07-195) to M.-F.A. and F. D., ARC NoA09/5/5003 to B.B.-d.P., ARC 4985 to C. B., Institut National du Cancer (INCa)-Canceropole Ile de France (melanoma network RS#13) to B.B.-deP., INCa-PNES rein to B. G., S.Ga. and S. R., INCa grant R08009AP to C. B., Fondation de France 2010 to R. B., INCa and Ligue National Contre le Cancer to I. D., Fond de maturation IGR and Fondation Gustave Roussy to B.B.-d.P., Societe Francaise de Dermatologie SDF2004 to R. B. and P. B., SFD2009 to B.B.-d.P., 2009 SGR 1337 from AGAUR, Generalitat de Catalunya, and FIS PS09/01393 from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain to S. P. and C. B., and personal donations from C. and N. de Paillerets and M.-H.Wagner. to B.B.-d.P. B.B-d.P. holds an INSERM Research Fellowship for hospital-based scientists. Work at the Centre National de Genotypage (CNG) and Centre d'Etude du Polymorphisme Humain (CEPH) was supported in part by INCa., Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -IFR50-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Apoptose, cancer et immunité ( U848 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Génétique, Institut de cancérologie Gustave Roussy, Villejuif, France, Institut Gustave Roussy ( IGR ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Laboratoire Electronique, Informatique et Image [UMR6303] ( Le2i ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-École Nationale Supérieure d'Arts et Métiers ( ENSAM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Cytokines et Immunologie des Tumeurs Humaines ( U753 ), INSTITUT CURIE, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Centre d'Etude du Polymorphisme Humain ( CEPH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Fondation Jean Dausset, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Unité de Recherche en Epidémiologie Nutritionnelle ( UREN ), Université Paris 13 ( UP13 ) -Institut National de la Recherche Agronomique ( INRA ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Université de Franche-Comté ( UFC ), Centre François Baclesse, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, CRLCC Eugène Marquis ( CRLCC ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP), Validation et identification de nouvelles cibles en oncologie ( VINCO ), Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Institut de Génomique d'Evry ( IG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Fondation Jean Dausset-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: multidisciplinary sciences, MESH : Germ-Line Mutation, SUMO protein, urologic and male genital diseases, medicine.disease_cause, MESH : Neoplasm Invasiveness, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH : Carcinoma, Renal Cell, 0302 clinical medicine, Gene Frequency, Cell Movement, MESH: Germ-Line Mutation, MESH : Cell Movement, MESH : Gene Frequency, MESH: Cell Movement, ComputingMilieux_MISCELLANEOUS, Genetics, 0303 health sciences, Multidisciplinary, MESH: Sumoylation, Melanoma, MESH : Sumoylation, MESH: Genetic Predisposition to Disease, renal carcinoma, MESH: Carcinoma, Renal Cell, Microphthalmia-associated transcription factor, MESH : Microphthalmia-Associated Transcription Factor, 3. Good health, germline mutation, 030220 oncology & carcinogenesis, MESH: Microphthalmia-Associated Transcription Factor, science and technology, MESH: Melanoma, sumo, MESH : Melanoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, Germline mutation, melanoma, MESH: Gene Frequency, Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, Neoplasm Invasiveness, Carcinoma, Renal Cell, neoplasms, Transcription factor, Germ-Line Mutation, 030304 developmental biology, Microphthalmia-Associated Transcription Factor, MESH: Humans, MESH : Humans, Sumoylation, MESH: Neoplasm Invasiveness, medicine.disease, HIF1A, cancer cells, Cancer research, MESH : Genetic Predisposition to Disease, Carcinogenesis
Abstract: International audience; So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (ΨKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.
Published: 2011
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29. High levels of antibodies against merkel cell polyomavirus identify a subset of patients with merkel cell carcinoma with better clinical outcome

Author: Gérard Lorette, Eve Maubec, Agnès Carlotti, Annabel Maruani, Marie-Françoise Avril, Maxime Fleury, Raphaël Cazal, Serge Guyétant, Mauro Tognon, Flore Rozenberg, Françoise Arnold, Antoine Touzé, Emmanuelle Le Bidre, François Aubin, Pierre Coursaget, Hélène Laude, Laboratoire Analyse, Géométrie et Applications (LAGA), Université Paris 8 Vincennes-Saint-Denis (UP8)-Centre National de la Recherche Scientifique (CNRS)-Institut Galilée-Université Paris 13 (UP13), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie, Hôpital Saint-Vincent de Paul, Laboratoire Analyse, Géométrie et Applications ( LAGA ), Université Paris 8 Vincennes-Saint-Denis ( UP8 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut Galilée-Centre National de la Recherche Scientifique ( CNRS ), Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Service de Dermatologie, Hôpital Cochin, AP-HP, Paris, Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Université de Franche-Comté ( UFC ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]
Subjects: Pathology, MESH: Chi-Square Distribution, MESH: Lymphatic Metastasis, MESH: Polyomavirus, MESH : Aged, MESH : Prospective Studies, MESH: Risk Assessment, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Merkel cell carcinoma, 0302 clinical medicine, MESH: Up-Regulation, MESH : Neoplasm Staging, MESH : Up-Regulation, MESH: Capsid Proteins, 0303 health sciences, MESH: Middle Aged, Antibody titer, food and beverages, MESH : Lymphatic Metastasis, MESH : Enzyme-Linked Immunosorbent Assay, MESH: Case-Control Studies, MESH : Polyomavirus, 3. Good health, Oncology, 030220 oncology & carcinogenesis, MESH: RNA, Viral, VIRUS, Antibody, MESH : Case-Control Studies, medicine.medical_specialty, MESH: Prognosis, 03 medical and health sciences, MESH : Middle Aged, MESH : Predictive Value of Tests, MESH : Aged, 80 and over, MESH: Kaplan-Meier Estimate, MESH: Humans, MESH : Chi-Square Distribution, MESH : Humans, MESH: Adult, MESH : Proportional Hazards Models, medicine.disease, MESH: Tumor Markers, Biological, MESH: Disease-Free Survival, MESH: Female, SKIN, MESH: Antibodies, Viral, Cancer Research, MESH : Capsid Proteins, Merkel cell polyomavirus, Human skin, antibody, immune system, outcome, MESH: Proportional Hazards Models, MESH: Aged, 80 and over, MESH: Risk Factors, MESH : Tumor Markers, Biological, INFECTION, EPIDEMIOLOGY, MESH : Female, MESH : Risk Assessment, MESH : Carcinoma, Merkel Cell, MESH: Aged, MESH : Prognosis, biology, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Neoplasm Staging, MESH : Adult, MESH : Risk Factors, MESH: Predictive Value of Tests, ETIOLOGY, MESH : Disease-Free Survival, MESH : Time Factors, circulatory and respiratory physiology, MESH : Antibodies, Viral, EXPRESSION, TISSUES, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Kaplan-Meier Estimate, medicine, MESH : RNA, Viral, MESH : France, 030304 developmental biology, Insect cell, business.industry, MESH: Skin Neoplasms, MESH : Skin Neoplasms, MESH: Time Factors, Cancer, MESH: Carcinoma, Merkel Cell, biology.organism_classification, MESH: Male, MESH: Prospective Studies, MESH: France, Geometric mean titer, MCV, biology.protein, business
Abstract: Purpose A new human polyomavirus, Merkel cell polyomavirus (MCV), was identified in 2008 in tumor tissue of patients with Merkel cell carcinoma (MCC), a relatively rare human skin cancer. In this study, we investigated patients with MCC and controls for the presence of antibodies against MCV and their association with clinical characteristics. Patients and Methods Antibodies against MCV were investigated by enzyme-linked immunosorbent assay in 68 patients with MCC and 82 controls using VP1 virus-like particles produced in insect cells. Results Antibodies against MCV were detected in all patients with MCC and in 85% of controls. However, high antibody titers (> 10,000) were rarely observed in controls (7.3%) and they were detected in 64.7% of patients with MCC (P < .001) in contrast to the absence of VP1 expression in tumor samples. In addition, the geometric mean titer of anti-MCV in patients with MCC was around 14 times higher than that observed in MCV-positive controls (P < .001) and was not correlated with tumor viral load. High antibody titers were not found to be associated with any subject or tumor characteristics, but better progression-free survival was observed in patients with high antibody titers (hazard ratio, 4.6; 95% CI, 1.7 to 12.2; P = .002). Conclusion High titers of MCV antibodies in a much higher proportion of patients with MCC than in controls confirmed the association between MCV infection and MCC. The findings also indicated that a better progression-free survival occurred in patients with high MCV antibody titers and suggested that there are at least two distinct etiologic causes of MCC.
Published: 2011
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30. Novel FH mutations in families with hereditary leiomyomatosis renal cell cancer (HLRCC) and in patients with isolated type 2 papillary renal cell carcinoma

Author: Catherine Dugast, Christelle Pruvost-Balland, Dan Lipsker, Nicolas Janin, Isabelle Coupier, Isabelle Mortemousque, Sophie Deveaux, Brigitte Gilbert-Dussardier, Laurence Faivre, Pierre Vabres, Emmanuel Van Glabeke, Hélène Dollfus, Min-Han Tan, Dominique Leroux, Pierre Rustin, Bernard Escudier, Marie-Françoise Avril, Joelle Roume, Veronica Cusin, Virginie Verkarre, Johny Bombled, Luc Thomas, Felicia Malthieu, Betty Gardie, Jean Feunteun, Darouna Kattygnarath, Jean -Baptiste Meric, Arnaud Mejean, Ghislaine Plessis, Olivier Caron, Victoria Perrier-Trudova, Stéphane Richard, Frédéric Caux, Virginie Joulin, Gilbert M. Lenoir, Abdelhamid Slama, Christine Maugard, Serena Rooker, Michel Barrois, Sandrine Lefevre, Brigitte Bressac-de Paillerets, Audrey Remenieras, Christine Theodore, Didier Bessis, Michelle Steinraths, Michel Field, Bruce Poppe, Yves Leport, Carol Cremin, Patrick Collignon, Barbara McGilliwray, Nadem Soufir, Bin Tean Teh, Cytokines et Immunologie des Tumeurs Humaines (U753), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hématopoïèse normale et pathologique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie, Hôpital de Bicêtre, AP-HP, Le Kremlin-Bicêtre, Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Gustave Roussy (IGR), Service de dermatologie [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13), Service de Génétique Médicale, Centre Hospitalier Intercommunal, Toulon, Service d'Oncogénétique et Génétique Médicale, BC Cancer Agency, Vancouver, Service de Génétique Médicale, Hôpital Civil, Strasbourg, Consultation d'Oncogénétique, CHU, Rennes, Département d'immunothérapie, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Genetic Services, Royal North Shore Hospital, St Leonards, Service de Génétique, CHU, Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Département de Génétique, CHU, Liège, Cabinet de Dermatologie, Vire, Service d'onco-hématologie et génétique, CHU Grenoble, Service de Dermatologie, Hôpital Civil, Strasbourg, Centre médico-chirurgical Atlantique, Puilboreau, Laboratoire de diagnostic génétique, Hôpital Universitaire de Strasbourg, Strasbourg, Service d'urologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Service de Génétique Médicale, Hôpital Bretonneau, Tours, Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Center for Medical Genetics, Universiteit Gent, Gand, Service de Dermatologie, Hôpital Saint Louis, AP-HP, Paris, Molecular Genetics Laboratory, Capital Coasts DHB, Wellington South, Consultation de Génétique Médicale, Hôpital Ambroise Paré, AP-HP, Boulogne, Consultation de Génétique, Hôpital Bichat-Claude Bernard, AP-HP, Paris, Division of Medical Genetics,Victoria General Hospital, Victoria, BC, Department of Medical Oncology, National Cancer Centre, Service d'Oncologie Médicale, Hôpital Foch, Suresnes, Service de Dermatologie, Centre Hospitalier Sud, Hospices Civils, Lyon, Service de Dermatologie (CHU de Dijon), Service d'Urologie, Hôpital André Grégoire, Service d'Onco-Hématologie, Centre Médical de Bligny, Briis sous Forges, CHU Necker - Enfants Malades [AP-HP], Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Centre Expert National Cancer Rares PREDIR, Service d'Urologie, CHU de Bicêtre, Le Kremlin-Bicêtre, Van Andel Research Institute, Grand Rapids, Michigan, Van Andel Institute [Grand Rapids], Génétique Oncologique EPHE, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, Peer, Hal, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], and Universiteit Gent = Ghent University (UGENT)
Subjects: Adult, Male, Proband, Skin Neoplasms, Genotype, Mutation, Missense, Biology, Bioinformatics, urologic and male genital diseases, Fumarate Hydratase, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, INDEL Mutation, Neoplastic Syndromes, Hereditary, Cell Line, Tumor, Leiomyomatosis, medicine, Genetics, Humans, Missense mutation, Molecular genetics, Frameshift Mutation, Carcinoma, Renal Cell, Germ-Line Mutation, Genetics (clinical), Aged, 030304 developmental biology, Gene Rearrangement, 0303 health sciences, Papillary renal cell carcinomas, Cancer, Middle Aged, medicine.disease, Penetrance, Kidney Neoplasms, Pedigree, 3. Good health, Codon, Nonsense, 030220 oncology & carcinogenesis, Mutation, Uterine Neoplasms, Cancer research, Cancer: urological, Female, Hereditary leiomyomatosis and renal cell carcinoma, Kidney cancer, Gene Deletion
Abstract: International audience; Background Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder predisposing humans to cutaneous and uterine leiomyomas; in 20% of affected families, type 2 papillary renal cell cancers (PRCCII) also occur with aggressive course and poor prognosis. HLRCC results from heterozygous germline mutations in the tumor suppressor fumarate hydratase (FH) gene. Methods As part of the French National Cancer Institute (INCa) "Inherited predispositions to kidney cancer" network, we performed sequence analysis and a functional study of FH in 56 families with clinically proven or suspected HLRCC and in 23 patients with isolated PRCCII (5 familial and 18 sporadic). Results We identified 32 different germline FH mutations (15 missense, six frameshifts, four nonsense, one deletion/insertion, five splice site and one complete deletion) in 40/56 (71.4%) families with proven or suspected HLRCC and in 4/23 (17.4%) probands with PRCCII alone, including 2 sporadic cases. Twenty-one of these were novel and all were demonstrated as deleterious by significant reduction of FH enzymatic activity. In addition, five asymptomatic parents in three families were confirmed as carrying disease-causing mutations. Conclusions This study identified and characterized 21 novel FH mutations and demonstrated that PRCCII can be the only one manifestation of HLRCC. Due to the incomplete penetrance of HLRCC, we propose to extend the FH mutation analysis to every patient with PRCCII occurring before 40 yrs of age or when renal tumor harbors characteristic histologic features, in order to discover previously ignored HLRCC-affected families.
Published: 2011
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31. The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma

Author: F, Lesueur, M, de Lichy, M, Barrois, G, Durand, J, Bombled, M-F, Avril, A, Chompret, F, Boitier, G M, Lenoir, B, Bressac-de Paillerets, Monique, Baccard, Bertrand, Bachollet, Pascaline, Berthet, Valérie, Bonadona, Jean-Marie, Bonnetblanc, Olivier, Caron, Jacqueline, Chevrant-Breton, Jean-François, Cuny, Stéphane, Dalle, Michèle, Delaunay, Liliane, Demange, Julie, De Quatrebarbes, Jean-François, Doré, Marc, Frénay, Jean-Pierre, Fricker, Marion, Gauthier-Villars, Paul, Gesta, Sophie, Giraud, Philippe, Gorry, Florent, Grange, Andrew, Green, Laetitia, Huiart, Nicolas, Janin, Pascal, Joly, Delphine, Kérob, Christine, Lasset, Dominique, Leroux, Jean-Marc, Limacher, Michel, Longy, Sandrine, Mansard, Karine, Marrou, Tanguy, Martin-Denavit, Christine, Mateus, Eve, Maubec, Laurence, Olivier-Faivre, Vincent, Orlandini, Pascal, Pujol, Bruno, Sassolas, Dominique, Stoppa-Lyonnet, Luc, Thomas, Pierre, Vabres, Laurence, Venat, Ewa, Wierzbicka, Hélène, Zattara, Groupe de Recherche en Economie Théorique et Appliquée (GREThA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Sect Mech Carcinogenesis, International Agency for Cancer Research (IACR), Génomes et cancer (GC (FRE2939)), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Vectorologie et transfert de gènes (VTG / UMR8121), Service de dermatologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de Génétique [Villejuif], Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hôpital Michallon, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Equipe de Recherche Médicale Appliquée (ERMA), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut de Génomique Fonctionnelle (IGF), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), Luxembourg Institute of Health (LIH), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hôpital pasteur [Colmar], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service de dermatologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Pathologie moléculaire des cancers, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)
Subjects: Male, Cancer Research, p14ARF, Exon, 0302 clinical medicine, CDKN2A, Tumor Suppressor Protein p14ARF, Multiplec ligation-dependent probe amplification, multiplex ligation-dependent probe amplification, Melanoma, Exome sequencing, ComputingMilieux_MISCELLANEOUS, Genetics, Aged, 80 and over, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, Exons, Middle Aged, 3. Good health, Pedigree, Melanoma-prone families, Oncology, 030220 oncology & carcinogenesis, Female, Chromosomes, Human, Pair 9, Molecular Sequence Data, Locus (genetics), Biology, 03 medical and health sciences, Germline mutation, p16INK4a, Humans, Point Mutation, Genetic Predisposition to Disease, Multiplex ligation-dependent probe amplification, Gene, neoplasms, Cyclin-Dependent Kinase Inhibitor p16, 030304 developmental biology, Aged, Base Sequence, Point mutation, Genes, p16, Genetics and Genomics, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Cancer research, KLHL9, Carrier Proteins, Gene Deletion, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; Mutations in two genes encoding cell cycle regulatory proteins have been shown to cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone families bear a point mutation in the CDKN2A locus at 9p21, which encodes two unrelated proteins, p16(INK4a) and p14(ARF). Rare mutations in CDK4 have also been linked to the disease. Although the CDKN2A gene has been shown to be the major melanoma predisposing gene, there remains a significant proportion of melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not been identified through direct exon sequencing. The purpose of this study was to assess the contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families using multiplex ligation-dependent probe amplification. We examined 214 patients from independent pedigrees with at least two CMM cases. All had been tested for CDKN2A and CDK4 point mutation, and 47 were found positive. Among the remaining 167 negative patients, one carried a novel genomic deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total mutations in this series (1 of 48), confirming that they explain a very small proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21, KLHL9, as being a major CMM gene.
Published: 2008
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32. Basal Cell Carcinoma in Gorlin’s Patients: a Matter of Fibroblasts-Led Protumoral Microenvironment?

Author: Thierry Magnaldo, Florence Brellier, Nicolas Sevenet, Martial Ruat, Elodie Burty-Valin, Sahar Al-Qaraghuli, Yannick Gache, Maria Goncalves-Maia, Sabine Scarzello, Sophie Rouanet, Stéphanie Barnay, Marie-Françoise Avril, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Génomes et cancer (GC (FRE2939)), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Evolution Paris Seine, Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), HAL-UPMC, Gestionnaire, Université Nice Sophia Antipolis (... - 2019) (UNS), and Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (... - 2019) (UNS)
Subjects: Keratinocytes, Patched Receptors, Pathology, medicine.medical_specialty, Skin Neoplasms, Tumor suppressor gene, Cellular differentiation, lcsh:Medicine, Receptors, Cell Surface, [SDV.CAN]Life Sciences [q-bio]/Cancer, Nevoid basal-cell carcinoma syndrome, Organ Culture Techniques, [SDV.CAN] Life Sciences [q-bio]/Cancer, Tumor Microenvironment, medicine, Humans, Basal cell carcinoma, Sonic hedgehog, lcsh:Science, Fibroblast, Cells, Cultured, Cell Proliferation, Tumor microenvironment, Multidisciplinary, integumentary system, biology, lcsh:R, Basal Cell Nevus Syndrome, Cell Differentiation, Fibroblasts, medicine.disease, Coculture Techniques, 3. Good health, Patched-1 Receptor, stomatognathic diseases, medicine.anatomical_structure, Carcinoma, Basal Cell, Culture Media, Conditioned, Mutation, Cancer research, biology.protein, lcsh:Q, Tumor Suppressor Protein p53, Keratinocyte, Research Article
Abstract: International audience; Basal cell carcinoma (BCC) is the commonest tumor in human. About 70% sporadic BCCs bear somatic mutations in the PATCHED1 tumor suppressor gene which encodes the receptor for the Sonic Hedgehog morphogen (SHH). PATCHED1 germinal mutations are associated with the dominant Nevoid Basal Cell Carcinoma Syndrome (NBCCS), a major hallmark of which is a high susceptibility to BCCs. Although the vast majority of sporadic BCCs arises exclusively in sun exposed skin areas, 40 to 50% BCCs from NBCCS patients develop in non photo-exposed skin. Since overwhelming evidences indicate that microenvironment may both be modified by- and influence the- epithelial tumor, we hypothesized that NBCCS fibroblasts could contribute to BCCs in NBCCS patients, notably those developing in non photo-exposed skin areas. The functional impact of NBCCS fibroblasts was then assessed in organotypic skin cultures with control keratinocytes. Onset of epidermal differentiation was delayed in the presence of primary NBCCS fibroblasts. Unexpectedly, keratinocyte proliferation was severely reduced and showed high levels of nuclear P53 in both organotypic skin cultures and in fibroblast-led conditioning experiments. However, in spite of increased levels of senescence associated β-galactosidase activity in keratinocytes cultured in the presence of medium conditioned by NBCCS fibroblasts, we failed to observe activation of P16 and P21 and then of bona fide features of senescence. Constitutive extinction of P53 in WT keratinocytes resulted in an invasive phenotype in the presence of NBCCS fibroblasts. Finally, we found that expression of SHH was limited to fibroblasts but was dependent on the presence of keratinocytes. Inhibition of SHH binding resulted in improved epidermal morphogenesis. Altogether, these data suggest that the repertoire of diffusible factors (including SHH) expressed by primary NBCCS fibroblasts generate a stress affecting keratinocytes behavior and epidermal homeostasis. Our findings suggest that defects in dermo/epidermal interactions could contribute to BCC susceptibility in NBCCS patients.
Published: 2015
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33. Prognostic Value of 25-hydroxyvitamin D3 Levels at Diagnosis and During Follow-up in Melanoma Patients

Author: Pierre Wolkenstein, Vincent Descamps, Philippe Saiag, Mathieu Boniol, Céleste Lebbé, Dominique Vitoux, Selim Aractingi, Philippe Autier, Philippe Aegerter, Miruna Dragomir, Elisa Funck-Brentano, Nicolas Dupin, Hôpital Ambroise Paré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie, Hôpital Saint-Louis, Service de Dermatologie, Hôpital Saint Louis, AP-HP, Paris, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Descartes - Paris 5 (UPD5), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie, Hôpital Bichat, AP-HP, International Prevention Research Institute (IPRI), Strathclyde Institute of Global Public Health at iPRI (SIGPH@iPRI), AP-HP Hôpital Ambroise Paré (Boulogne-Billancourt), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique ( VIMA ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Versailles–St. Quentin, Faculté de Médecine Paris‐Ile‐de‐France‐Ouest, Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], International Prevention Research Institute ( IPRI ), and Strathclyde Institute of Global Public Health at iPRI ( SIGPH@iPRI )
Subjects: Cancer Research, medicine.medical_specialty, Gastroenterology, RS, RC0254, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Prospective cohort study, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, Proportional hazards model, business.industry, Hazard ratio, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Odds ratio, Confidence interval, 3. Good health, Surgery, Oncology, Quartile, 030220 oncology & carcinogenesis, Predictive value of tests, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Body mass index
Abstract: Saiag, Philippe Aegerter, Philippe Vitoux, Dominique Lebbe, Celeste Wolkenstein, Pierre Dupin, Nicolas Descamps, Vincent Aractingi, Selim Funck-Brentano, Elisa Autier, Philippe Dragomir, Miruna Boniol, Mathieu eng Research Support, Non-U.S. Gov't 2015/09/18 06:00 J Natl Cancer Inst. 2015 Sep 15;107(12):djv264. doi: 10.1093/jnci/djv264. Print 2015 Dec.; International audience; BACKGROUND: A low 25-hydroxyvitamin D3 (25(OH)D3) serum concentration at melanoma diagnosis might be associated with worse survival. We prospectively studied the prognostic value of 25(OH)D3 at diagnosis and during follow-up. METHODS: MelanCohort is a cohort of invasive melanoma patients. Serum 25(OH)D3 was measured by mass spectrometry and standardized on month of blood drawn, age, sex, and body mass index (BMI). Role of 25(OH)D3 levels and risk of relapse was analyzed in a Cox proportional hazards model adjusting for age, sex, BMI, and American Joint Committee on Cancer (AJCC) stage. All statistical tests were two-sided. RESULTS: One thousand one hundred seventy-one patients were included. 25(OH)D3 levels at diagnosis (median = 49.0 nmol/L) were inversely correlated with prognostic factors such as AJCC stage (P < .001 Kruskal-Wallis), Breslow's thickness (P < .001 Spearman correlation), and ulceration (P < .001 Kruskal-Wallis), but not with risk of relapse. Changes in 25(OH)D3 levels during follow-up were associated with worse prognosis: With a third quartile Q3 of average change per year (-0.30 to 4.60 nmol/L/Y) used as reference, hazard ratios for the first, second, and fourth quarters were 1.94 (95% confidence interval [CI] = 1.36 to 2.76), 1.23 (95% CI = 0.85 to 1.78), and 1.61 (95% CI = 1.14 to 2.28), respectively. In sensitivity analyses, no changes were observed either by AJCC stage, number of 25(OH)D3 measures performed, or by 25(OH)D3 level at baseline. No evidence of reverse causation was identified. Analyses performed on overall survival yielded similar results. CONCLUSIONS: We show that 25(OH)D3 variation during follow-up is an independent melanoma prognostic marker, but not its level at diagnosis. Previously reported associations between low 25(OH)D3 level at diagnosis and poor prognosis seem to be due to insufficient adjustment for prognostic factors.
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34. Germline CDKN2A /P16INK4A mutations contribute to genetic determinism of sarcoma

Author: Gaëlle Pierron, Gaëlle Bougeard, Jean-Baptiste Demoulin, Axel Lecesne, Daniel Pissaloux, Emeline Bollaert, Thierry Frebourg, Brigitte Bressac-de Paillerets, Serge Koscielny, Capucine Delnatte, Jean-Yves Scoazec, Isaure Chauvot de Beauchêne, Jennifer H. Barrett, Philippe Terrier, Arnaud de la Fouchardière, Graham J. Mann, Isabelle Coupier, Nelleke A. Gruis, Jean Feunteun, Birama N’Diaye, Alexander M.M. Eggermont, Dominique Stoppa-Lyonnet, Olivier Ingster, Luba Tchertanov, Rosine Guimbaud, Patrick R. Benusiglio, Olivier Caron, Fanélie Jouenne, Marie-Françoise Avril, Marion Gauthier-Villars, Remco van Doorn, Julia Newton-Bishop, Vincent Caumette, Mark Harland, Amélie Velghe, Odile Cabaret, Immunologie intégrative des tumeurs (UMR 1186), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Technische Universität München [München] (TUM), De Duve Institute, Université Catholique de Louvain, Service de dermatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hematopoïèse et Cellules Souches (U362), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National du Cancer [Boulogne Billancourt] (INC), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Service de Pathologie [Centre Leon Berard], Centre Léon Bérard [Lyon], Service de génétique moléculaire, pharmacogénétique et hormonologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Inserm UMR837 Team 5, Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Centre for Atmospheric Science [Leeds] (NCAS), Natural Environment Research Council (NERC), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Leeds Institute of Cancer and Pathology [U.K.], Leiden University Medical Center (LUMC), Service de génétique, Institut Curie Paris, Unit of Somatic Genomics, Department of Genetics, Institut Curie, Paris Sciences et Lettres (PSL), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gastro - Entérologie et Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], CRLCC René Gauducheau, Tumeurs endocrines digestives : mécanismes de la tumorigenèse et de la progression tumorale, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématopoïèse normale et pathologique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Centre de Mathématiques et de Leurs Applications (CMLA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Computational Algorithms for Protein Structures and Interactions (CAPSID), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Weastmead Institute for Medical Research and Melanoma Institute, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Génétique Oncologique, Institut Curie [Paris], Unité d'Oncogénétique, CRLCC Val d'Aurelle - Paul Lamarque, Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Centre René Gauducheau, Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institut Gustave Roussy ( IGR ), Immunologie intégrative des tumeurs ( UMR 1186 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Technical University of Munich ( TUM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université d'Angers ( UA ) -CHU Angers, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de biostatistique et d'épidémiologie ( SBE ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), INSTITUT CURIE, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Stabilité Génétique et Oncogenèse ( UMR 8200 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Mathématiques et de Leurs Applications ( CMLA ), École normale supérieure - Cachan ( ENS Cachan ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHAUVOT DE BEAUCHENE, Isaure, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Universiteit Leiden
Subjects: 0301 basic medicine, medicine.medical_specialty, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.CAN]Life Sciences [q-bio]/Cancer, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, PDGFRA, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Germline, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Loss of heterozygosity, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, CDKN2A, Molecular genetics, Genetics, medicine, Genetic epidemiology, Hereditary Melanoma, neoplasms, Connective tissue disease, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Cancer: dermatological, digestive system diseases, 3. Good health, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, Cancer research, Sarcoma, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract: International audience; BACKGROUND: Sarcomas are rare mesenchymal malignancies whose pathogenesis is poorly understood; both environmental and genetic risk factors could contribute to their aetiology.METHODS AND RESULTS: We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation in CDKN2A tumour suppressor gene. We searched for individuals with sarcoma among 474 melanoma-prone families with a CDKN2A-/+ genotype and for CDKN2A mutations in 190 TP53-negative LFL families where the index case was a sarcoma. Including the initial family, eight independent sarcoma cases carried a germline mutation in the CDKN2A/p16INK4A gene. In five out of seven formalin-fixed paraffin-embedded sarcomas, heterozygosity was lost at germline CDKN2A mutations sites demonstrating complete loss of function. As sarcomas are rare in CDKN2A/p16INK4A carriers, we searched in constitutional WES of nine carriers for potential modifying rare variants and identified three in platelet-derived growth factor receptor (PDGFRA) gene. Molecular modelling showed that two never-described variants could impact the PDGFRA extracellular domain structure.CONCLUSION: Germline mutations in CDKN2A/P16INK4A, a gene known to predispose to hereditary melanoma, pancreatic cancer and tobacco-related cancers, account also for a subset of hereditary sarcoma. In addition, we identified PDGFRA as a candidate modifier gene
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35. Extensive Necrotic Purpura in Levamisole-Adulterated Cocaine Abuse - A Case Report.

Author: Le Garff E, Tournel G, Becquart C, Cottencin O, Dupin N, Delaporte E, and Hedouin V
Subjects: Adult, Female, Humans, Skin, Cocaine chemistry, Cocaine-Related Disorders, Drug Contamination, Levamisole chemistry, Purpura chemically induced
Abstract: Levamisole, which is used as an adulterated compound of cocaine, is currently being seen year after year in cocaine intoxication. For a few cases in the last decade, necrotic purpura and neutropenia after levamisole/cocaine intoxication have been described in the medical community. Herein, we present an original case of levamisole intoxication of a 40-year-old woman who smoked heroin and cocaine few during a month. She rapidly presented an extensive necrotic purpura of the nose, cheeks and extremities (lower and upper), and immunologic reactions (positive anti-MPO and anti-HNE). Levamisole was detected on hairs with ultra-high performance liquid chromatography and tandem mass spectrometry. The case reports also a probable cocaine supplier deceit, which bring pure drug for hospital investigation after the intoxication of his client. The intoxicated woman had survived with several skin and chronic pain complications. That case recalls the knowledge about levamisole with a short review of the forensic literature., (© 2016 American Academy of Forensic Sciences.)
Published: 2016
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36. [Cranial fasciitis of childhood].

Author: Foureur N, Enjolras O, Boccon-Gibod L, Wetterwald E, Diner P, and Escande JP
Subjects: Female, Humans, Infant, Fasciitis pathology, Scalp Dermatoses pathology
Abstract: Introduction: A nodule of the scalp in a child of less than eleven years should evoke a cranial fasciitis among other serious diagnoses., Observation: A four-month old infant had a firm and pink nodule at the left parietal level, exhibiting a slow growth since two months. It was excised. The pathologic sample showed spindle-shaped cells within a myxoïde matrix, with a strong reactivity for smooth muscle actin (immunohistochemical analysis). Diagnosis of cranial fasciitis was made. Due to the results of pathology, it was possible to rule out the diagnosis of sarcoma, therefore, no complementary work-up was performed. Evolution was favorable., Discussion: Cranial fasciitis is a diagnosis to be considered when confronted with a firm nodule of the scalp in a infant or a young child, with or without bone involvement. This is a benign lesion but worrying pathological signs may exist, making diagnosis of benignity difficult. Exeresis of the lesion, even incomplete, protects the child from possible recurrence. Evolution is always good.
Published: 2002

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