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1. Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma

Author: Rana Salam, Alexa Saliou, Franck Bielle, Mathilde Bertrand, Christophe Antoniewski, Catherine Carpentier, Agusti Alentorn, Laurent Capelle, Marc Sanson, Emmanuelle Huillard, Léa Bellenger, Justine Guégan, and Isabelle Le Roux
Subjects: Science
Abstract: Senescence can have beneficial and detrimental impact on cancer progression depending on the cellular context. Here the authors show that NRF2 regulates the senescence phenotype in malignant cells which consequently contribute to glioblastoma progression.
Published: 2023
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2. Identification of growth hormone receptor as a relevant target for precision medicine in low‐EGFR expressing glioblastoma

Author: Maïté Verreault, Irma Segoviano Vilchis, Shai Rosenberg, Nolwenn Lemaire, Charlotte Schmitt, Jérémy Guehennec, Louis Royer‐Perron, Jean‐Léon Thomas, TuKiet T. Lam, Florent Dingli, Damarys Loew, François Ducray, Sophie Paris, Catherine Carpentier, Yannick Marie, Florence Laigle‐Donadey, Audrey Rousseau, Natascha Pigat, Florence Boutillon, Franck Bielle, Karima Mokhtari, Stuart J. Frank, Aurélien deReyniès, Khê Hoang‐Xuan, Marc Sanson, Vincent Goffin, and Ahmed Idbaih
Subjects: cell migration, comparative analysis, glioblastoma, oncogenicity, pre‐clinical models, therapeutic target, Medicine (General), R5-920
Abstract: Abstract Objective New therapeutic approaches are needed to improve the prognosis of glioblastoma (GBM) patients. Methods With the objective of identifying alternative oncogenic mechanisms to abnormally activated epidermal growth factor receptor (EGFR) signalling, one of the most common oncogenic mechanisms in GBM, we performed a comparative analysis of gene expression profiles in a series of 54 human GBM samples. We then conducted gain of function as well as genetic and pharmocological inhibition assays in GBM patient‐derived cell lines to functionnally validate our finding. Results We identified that growth hormone receptor (GHR) signalling defines a distinct molecular subset of GBMs devoid of EGFR overexpression. GHR overexpression was detected in one third of patients and was associated with low levels of suppressor of cytokine signalling 2 (SOCS2) expression due to SOCS2 promoter hypermethylation. In GBM patient‐derived cell lines, GHR signalling modulates the expression of proteins involved in cellular movement, promotes cell migration, invasion and proliferation in vitro and promotes tumourigenesis, tumour growth, and tumour invasion in vivo. GHR genetic and pharmacological inhibition reduced cell proliferation and migration in vitro. Conclusion This study pioneers a new field of investigation to improve the prognosis of GBM patients.
Published: 2022
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3. The level of activity of the alternative lengthening of telomeres correlates with patient age in IDH-mutant ATRX-loss-of-expression anaplastic astrocytomas

Author: Nathalie Grandin, Bruno Pereira, Camille Cohen, Pauline Billard, Caroline Dehais, Catherine Carpentier, Ahmed Idbaih, Franck Bielle, François Ducray, Dominique Figarella-Branger, Jean-Yves Delattre, Marc Sanson, Patrick Lomonte, Delphine Poncet, Pierre Verrelle, Michel Charbonneau, and POLA network
Subjects: Anaplastic astrocytoma, Secondary glioblastoma, Alternative lengthening of telomeres, IDH1/2 mutations, ATRX loss of expression, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract All cancer cells need to maintain functional telomeres to sustain continuous cell division and proliferation. In human diffuse gliomas, functional telomeres are maintained due either to reactivation of telomerase expression, the main pathway in most cancer types, or to activation of a mechanism called the alternative lengthening of telomeres (ALT). The presence of IDH1/2 mutations (IDH-mutant) together with loss of ATRX expression (ATRX-lost) are frequently associated with ALT in diffuse gliomas. However, detection of ALT, and a fortiori its quantification, are rarely, if ever, measured in neuropathology laboratories. We measured the level of ALT activity using the previously described quantitative “C-circle” assay and analyzed it in a well characterized cohort of 104 IDH-mutant and ATRX-lost adult diffuse gliomas. We report that in IDH-mutant ATRX-lost anaplastic astrocytomas, the intensity of ALT was inversely correlated with age (p
Published: 2019
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4. Somatostatin receptor 2A protein expression characterizes anaplastic oligodendrogliomas with favorable outcome

Author: Romain Appay, Emeline Tabouret, Mehdi Touat, Catherine Carpentier, Carole Colin, François Ducray, Ahmed Idbaih, Karima Mokhtari, Emmanuelle Uro-Coste, Caroline Dehais, Dominique Figarella-Branger, and the POLA network
Subjects: Somatostatin receptor subtype 2A (SSTR2A), Glioma, Biomarker, Therapeutic target, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Diffuse gliomas are classified according to the 2016 WHO Classification of Tumors of the Central Nervous System, which now defines entities by both histology and molecular features. Somatostatin receptor subtype 2A (SSTR2A) expression has been reported in various solid tumors as associated with favorable outcomes. Its expression has been reported in gliomas with uncertain results regarding its prognostic value. The objective of this study was to assess the prognostic impact of SSTR2A protein expression in a large cohort of grade III and IV gliomas classified according to the updated 2016 WHO classification. We further validated our result with an independent cohort of low grade glioma using dataset generated by The Cancer Genome Atlas (TCGA) Research Network. We analyzed clinical and molecular data from 575 patients. SSTR2A protein expression was evaluated using immunohistochemistry on tissue microarrays. High expression of SSTR2A protein associated with the anaplastic oligodendroglioma IDH-mutant and 1p/19q-codeleted subgroup (p
Published: 2018
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5. Integrated multi-omics analysis of oligodendroglial tumours identifies three subgroups of 1p/19q co-deleted gliomas

Author: Aurélie Kamoun, Ahmed Idbaih, Caroline Dehais, Nabila Elarouci, Catherine Carpentier, Eric Letouzé, Carole Colin, Karima Mokhtari, Anne Jouvet, Emmanuelle Uro-Coste, Nadine Martin-Duverneuil, Marc Sanson, Jean-Yves Delattre, Dominique Figarella-Branger, Aurélien de Reyniès, François Ducray, and POLA network
Subjects: Science
Abstract: Oligodendroglial tumours are characterized into three different molecular subtypes. Here, the authors use genomic data to identify a further three subgroups of 1p/19q co-deleted tumours and demonstrate an association with an aggressive phenotype.
Published: 2016
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6. Correction: SNP Array Analysis Reveals Novel Genomic Abnormalities Including Copy Neutral Loss of Heterozygosity in Anaplastic Oligodendrogliomas.

Author: Ahmed Idbaih, François Ducray, Caroline Dehais, Célia Courdy, Catherine Carpentier, Simon de Bernard, Emmanuelle Uro-Coste, Karima Mokhtari, Anne Jouvet, Jérôme Honnorat, Olivier Chinot, Carole Ramirez, Patrick Beauchesne, Alexandra Benouaich-Amiel, Joël Godard, Sandrine Eimer, Fabrice Parker, Emmanuelle Lechapt-Zalcman, Philippe Colin, Delphine Loussouarn, Thierry Faillot, Phong Dam-Hieu, Selma Elouadhani-Hamdi, Luc Bauchet, Olivier Langlois, Caroline Le Guerinel, Denys Fontaine, Elodie Vauleon, Philippe Menei, Marie Janette Motsuo Fotso, Christine Desenclos, Pierre Verrelle, François Ghiringhelli, Georges Noel, François Labrousse, Antoine Carpentier, Frédéric Dhermain, Jean-Yves Delattre, and Dominique Figarella-Branger
Subjects: Medicine, Science
Published: 2013
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7. SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas.

Author: Ahmed Idbaih, François Ducray, Caroline Dehais, Célia Courdy, Catherine Carpentier, Simon de Bernard, Emmanuelle Uro-Coste, Karima Mokhtari, Anne Jouvet, Jérôme Honnorat, Olivier Chinot, Carole Ramirez, Patrick Beauchesne, Alexandra Benouaich-Amiel, Joël Godard, Sandrine Eimer, Fabrice Parker, Emmanuelle Lechapt-Zalcman, Philippe Colin, Delphine Loussouarn, Thierry Faillot, Phong Dam-Hieu, Selma Elouadhani-Hamdi, Luc Bauchet, Olivier Langlois, Caroline Le Guerinel, Denys Fontaine, Elodie Vauleon, Philippe Menei, Marie Janette Motsuo Fotso, Christine Desenclos, Pierre Verrelle, François Ghiringhelli, Georges Noel, François Labrousse, Antoine Carpentier, Frédéric Dhermain, Jean-Yves Delattre, Dominique Figarella-Branger, and POLA Network
Subjects: Medicine, Science
Abstract: Anaplastic oligodendrogliomas (AOD) are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19)(q10;p10), IDH1, IDH2, CIC and FUBP1 mutations).To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA)," has been supported by the Institut National du Cancer (InCA). Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples) were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH) inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD.
Published: 2012
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8. Mapping the DeFi Crime Landscape: An Evidence-based Picture.

Author: Catherine Carpentier-Desjardins, Masarah Paquet-Clouston, Stefan Kitzler, and Bernhard Haslhofer
Published: 2023
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9. Incidence and Characteristics of Pseudoprogression in IDH-mutant High-Grade Gliomas: A POLA Network Study

Author: Antoine Seyve, Caroline Dehais, Olivier Chinot, Apolline Djelad, Elisabeth Cohen-Moyal, Charlotte Bronnimann, Carole Gourmelon, Evelyne Emery, Philippe Colin, Mathieu Boone, Elodie Vauléon, Olivier Langlois, Anna-Luisa di Stefano, Romuald Seizeur, François Ghiringhelli, Anne D’Hombres, Loic Feuvret, Jacques Guyotat, Laurent Capelle, Catherine Carpentier, Louis Garnier, Jérôme Honnorat, David Meyronet, Karima Mokhtari, Dominique Figarella-Branger, François Ducray, Hospices Civils de Lyon, Departement de Neurologie (HCL), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Bordeaux [Bordeaux], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service de Neurochirurgie [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), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Culture et Environnements, Préhistoire, Antiquité, Moyen-Age (CEPAM), 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)-Université Côte d'Azur (UCA), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hospices Civils de Lyon (HCL), Institut NeuroMyoGène (INMG), 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 de Référence Maladie Rare 'Syndromes neurologiques Paranéoplasiques', Hospices Civils de Lyon (HCL)-Hopital Neurologique, and Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
Subjects: Cancer Research, High-grade glioma, Oncology, pseudoprogression, Neurology (clinical), IDH-mutant, chemotherapy, radiotherapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Incidence and characteristics of pseudoprogression in isocitrate dehydrogenase-mutant high-grade gliomas (IDHmt HGG) remain to be specifically described. Methods We analyzed pseudoprogression characteristics and explored the possibility of pseudoprogression misdiagnosis in IDHmt HGG patients, treated with radiotherapy (RT) (with or without chemotherapy [CT]), included in the French POLA network. Pseudoprogression was analyzed in patients with MRI available for review (reference cohort, n = 200). Pseudoprogression misdiagnosis was estimated in this cohort and in an independent cohort (control cohort, n = 543) based on progression-free survival before and after first progression. Results In the reference cohort, 38 patients (19%) presented a pseudoprogression after a median time of 10.5 months after RT. Pseudoprogression characteristics were similar across IDHmt HGG subtypes. In most patients, it consisted of the appearance of one or several infracentimetric, asymptomatic, contrast-enhanced lesions occurring within 2 years after RT. The only factor associated with pseudoprogression occurrence was adjuvant PCV CT. Among patients considered as having a first true progression, 7 out of 41 (17%) in the reference cohort and 35 out of 203 (17%) in the control cohort were retrospectively suspected to have a misdiagnosed pseudoprogression. Patients with a misdiagnosed pseudoprogression were characterized by a time to event and an outcome similar to that of patients with a pseudoprogression but presented with larger and more symptomatic lesions. Conclusion In patients with an IDHmt HGG, pseudoprogression occurs later than in IDH-wildtype glioblastomas and seems not only frequent but also frequently misdiagnosed. Within the first 2 years after RT, the possibility of a pseudoprogression should be carefully considered.
Published: 2023

10. Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma

Author: Rana Salam, Alexa Saliou, Franck Bielle, Mathilde Bertrand, Christophe Antoniewski, Catherine Carpentier, Agusti Alentorn, Laurent Capelle, Marc Sanson, Emmanuelle Huillard, Léa Bellenger, Justine Guégan, Isabelle Le Roux, 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neuropathologie [CHU Pitié Salpêtrière], 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 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), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Français de Bioinformatique (IFB-CORE), Institut National de Recherche en Informatique et en Automatique (Inria)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], LE ROUX, Isabelle, CHU Charles Foix [AP-HP], CNRS, INSERM, ICM, Ligue Contre le Cancer, comité île de France, Fondation ARC pour la recherche sur la Cancer, SIRIC-CURAMUS, and Ligue Nationale Contre le Cancer
Subjects: [SDV] Life Sciences [q-bio], Multidisciplinary, Brain Tumor, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Microenvironnement Tumoral, scRNAseq, General Chemistry, Senescence, Mice model, General Biochemistry, Genetics and Molecular Biology
Abstract: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, yet it remains refractory to systemic therapy. Elimination of senescent cells has emerged as a promising new treatment approach against cancer. Here, we investigated the contribution of senescent cells to GBM progression. Senescent cells are identified in patient and mouse GBMs. Partial removal of p16Ink4a-expressing malignant senescent cells, which make up less than 7 % of the tumor, modifies the tumor ecosystem and improves the survival of GBM-bearing female mice. By combining single cell and bulk RNA sequencing, immunohistochemistry and genetic knockdowns, we identify the NRF2 transcription factor as a determinant of the senescent phenotype. Remarkably, our mouse senescent transcriptional signature and underlying mechanisms of senescence are conserved in patient GBMs, in whom higher senescence scores correlate with shorter survival times. These findings suggest that senolytic drug therapy may be a beneficial adjuvant therapy for patients with GBM.
Published: 2022

11. The TeloDIAG: how telomeric parameters can help in glioma rapid diagnosis and liquid biopsy approaches

Author: C Guerriau, Delphine Maucort-Boulch, Pauline Billard, Pierre Verrelle, Michel Charbonneau, Ruth Rimokh, Catherine Carpentier, Delphine Poncet, Dominique Figarella-Branger, François Ducray, David Meyronet, Patrick Lomonte, Nathalie Grandin, N Dufay, Marc Barritault, P Kantapareddy, Caroline Dehais, F Juillard, Service de Biostatistiques [Lyon], Hospices Civils de Lyon (HCL), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service d’Anatomie Pathologique et de Neuropathologie, APHM, Hôpital de la Timone, and Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: Oncology, Telomerase, medicine.medical_specialty, X-linked Nuclear Protein, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Internal medicine, Glioma, medicine, Humans, Liquid biopsy, neoplasms, Grading (tumors), ComputingMilieux_MISCELLANEOUS, ATRX, business.industry, Brain Neoplasms, Liquid Biopsy, Astrocytoma, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Hematology, Telomere, medicine.disease, Isocitrate Dehydrogenase, nervous system diseases, Isocitrate dehydrogenase, Oligodendroglioma, business
Abstract: Background In glioma, TERT promoter mutation and loss of ATRX (ATRX loss) are associated with reactivation of telomerase or alternative lengthening of telomeres (ALT), respectively, i.e. the two telomere maintenance mechanisms (TMM). Strangely, 25% of gliomas have been reported to display neither or both of these alterations. Materials and methods The C-circle (CC) assay was adapted to tumor (formalin-fixed paraffin-embedded and frozen) and blood samples to investigate the TMM. Results We constructed a CC-based algorithm able to identify the TMM and reported a sensitivity of 100% and a specificity of 97.3% (n = 284 gliomas). By combining the TMM, the mutational status of the isocitrate dehydrogenase 1/2 (IDH) gene (IDHmt), and the histological grading, we propose a new classification tool: TeloDIAG. This classification defined five subtypes: tOD, tLGA, tGBM_IDHmt, tGBM, and tAIV, corresponding to oligodendroglioma, IDHmt low-grade astrocytoma, IDHmt glioblastoma, and IDHwt glioblastoma (GBM), respectively; the last class gathers ALT+ IDHwt gliomas that tend to be related to longer survival (21.2 months) than tGBM (16.5 months). The TeloDIAG was 99% concordant with the World Health Organization classification (n = 312), and further modified the classification of 55 of 144 (38%) gliomas with atypical molecular characteristics. As an example, 14 of 69 (20%) of TERTwt, ATRXwt, and IDHwt GBM were actually tAIV. Outstandingly, CC in blood sampled from IDHmt astrocytoma patients was detected with a sensitivity of 56% and a specificity of 97% (n = 206 gliomas and 30 healthy donors). Conclusion The TeloDIAG is a new, simple, and effective tool helping in glioma diagnosis and a promising option for liquid biopsy.
Published: 2021

12. Radiotherapy Plus Procarbazine, Lomustine, and Vincristine Versus Radiotherapy Plus Temozolomide for IDH‐Mutant Anaplastic Astrocytoma: A Retrospective Multicenter Analysis of the French POLA Cohort

Author: Vincent Esteyrie, Caroline Dehais, Elodie Martin, Catherine Carpentier, Emmanuelle Uro-Coste, Dominique Figarella-Branger, Charlotte Bronniman, Damien Pouessel, Delphine Larrieu Ciron, François Ducray, Elizabeth Cohen-Jonathan Moyal, and Pola Network
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Vincristine, Astrocytoma, Procarbazine, 03 medical and health sciences, 0302 clinical medicine, Lomustine, Internal medicine, PCV Regimen, Antineoplastic Combined Chemotherapy Protocols, medicine, Temozolomide, Humans, Neuro‐Oncology, Retrospective Studies, business.industry, Brain Neoplasms, medicine.disease, Chemotherapy regimen, 3. Good health, Regimen, 030220 oncology & carcinogenesis, business, 030217 neurology & neurosurgery, Anaplastic astrocytoma, medicine.drug
Abstract: Background IDH-mutant anaplastic astrocytomas (AAs) are chemosensitive tumors for which the best choice of adjuvant chemotherapy between procarbazine, lomustine, and vincristine (PCV) or temozolomide (TMZ) after radiotherapy (RT) remains unclear. Methods In a large cohort of patients with histologically proven 2016 World Health Organization classification AA with IDH1/2 mutations included in the French national POLA cohort (n = 355), the primary objective was to compare progression-free survival (PFS) between the two treatment regimens (n = 311). Secondary endpoints were overall survival (OS), progression type, pseudoprogression rate, and toxicity. Results The 4-year PFS in the RT + PCV arm was 70.8% versus 53.5% in the RT + TMZ arm, with a hazard ratio (HR) of 0.58 (95% confidence interval [CI], 0.38–0.87; p = .0074) in univariable analysis and 0.63 (95% CI, 0.41–0.97; p = .0348) in multivariable analysis. The 4-year OS in the RT + PCV arm was 84.3% versus 76.6% in the RT + TMZ arm, with an HR of 0.57 (95% CI, 0.30–1.05; p = .0675) in univariable analysis. Toxicity was significantly higher in the RT + PCV arm with more grade ≥3 toxicity (46.7% vs. 8.6%, p < .0001). Conclusion RT + PCV significantly improved PFS compared with RT + TMZ for IDH-mutant AA. However, RT + TMZ was better tolerated. Implications for Practice In the absence of fully conducted randomized trials comparing procarbazine, lomustine, and vincristine (PCV) with temozolomide (TMZ) in adjuvant treatment after radiotherapy (RT) for the management of IDH-mutant anaplastic astrocytoma (AA) and a similar level of evidence, these two chemotherapies are both equally recommended in international guidelines. This study in a national cohort of IDH-mutant AA defined according the 2016 World Health Organization (WHO) classification shows for the first time that the RT + PCV regimen significantly improves progression-free survival in comparison with the RT + TMZ regimen. Even if at the time of analysis the difference in overall survival was not significant, this result provides new evidence for the debate about the chemotherapy regimen to prescribe in adjuvant treatment to RT for WHO 2016 IDH-mutant AA.
Published: 2021

13. OS02.6.A The TeloDIAG: How telomeric parameters can help in glioma rapid diagnosis and liquid biopsies approaches

Author: Ruth Rimokh, David Meyronet, Pierre Verrelle, D A Poncet, Nathalie Grandin, C Guerriau, P Kantapareddy, Caroline Dehais, François Ducray, Michel Charbonneau, F Juillard, Pauline Billard, Catherine Carpentier, D Maucort-Boulch, Dominique Figarella-Branger, Marc Barritault, and P Lomonte
Subjects: Cancer Research, Telomerase, Astrocytoma, Biology, medicine.disease, nervous system diseases, Telomere, Isocitrate dehydrogenase, Oncology, Glioma, Mutation (genetic algorithm), medicine, Cancer research, Neurology (clinical), Oligodendroglioma, Liquid biopsy, neoplasms
Abstract: BACKGROUND The integration of molecular markers into the WHO 2016 classification has clarified the complex diagnosis of gliomas. Among these biomarkers, the TERT promoter mutation and the loss of ATRX (ATRX loss) are mutually exclusive alterations associated with re-activation of telomerase or alternative lengthening of telomeres (ALT), respectively. Strangely, 25% of gliomas display neither or both these alterations, a situation referred to as abnormal telomere maintenance mechanism (aTMM). MATERIAL AND METHODS To investigate the TMM actually involved in gliomas, the C-circle (CC) assay was adapted to tumor (FFPE and frozen) samples. RESULTS We constructed a CC-based algorithm able to identify the TMM of 284 gliomas with either TERT or ATRX alteration, with a sensitivity of 100% and a specificity of 97.3%, and succeeded in deciphering the TMM involved in 122 aTMM gliomas. Additionally, the combination of the TMM, the mutational status of the Isocitrate dehydrogenase 1/2 (IDH) gene, and the histological grading was used as base for a new classification: TeloDIAG. Six subtypes are defined in this classification: tOD, tLGA, tGBM_IDHmt, tGBM, and tAIV, corresponding to oligodendroglioma, IDHmt low grade astrocytoma, IDHmt glioblastoma, and IDHwt glioblastoma, respectively, the last class gathers ALT+ IDHwt glioma. The TeloDIAG diagnosis is 99% concordant with the WHO classification for glioma displaying typical molecular characteristics (N=312). It modified the classification of 38% (N=156) discordant tumors, such as IDHwt Astrocytoma, aTMM tumors, or gliomas with unexpected TMM (e.g. TERTwt oligodendroglioma, ATRX loss GBM). Interestingly, 20% (N=69) of TERTwt, ATRXwt, or IDHwt GBM were actually tAIV, which is remarkable as tAIV-glioma patients’ survival tended to be longer (21.2 months) than tGBM patients’ survival (16.5 months). Importantly, CC in blood sampled from IDHmt astrocytoma patients was detected with a sensitivity of 56% and a specificity of 95% (N = 206). CONCLUSION In sum, the TeloDIAG is a new, simple, and efficient tool helping in glioma diagnosis and a promising option for liquid biopsy
Published: 2021

14. The level of activity of the alternative lengthening of telomeres correlates with patient age in IDH-mutant ATRX-loss-of-expression anaplastic astrocytomas

Author: Pierre Verrelle, Nathalie Grandin, Bruno Pereira, Ahmed Idbaih, Delphine Poncet, François Ducray, Franck Bielle, Pauline Billard, Patrick Lomonte, Jean-Yves Delattre, Dominique Figarella-Branger, Marc Sanson, Caroline Dehais, Catherine Carpentier, Camille Cohen, Michel Charbonneau, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Université de Caen Normandie (UNICAEN), Normandie Université (NU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), 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), 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), 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), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Cancer Resistance Exploring and Targeting (CREaT), Université d'Auvergne - Clermont-Ferrand I (UdA), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Pola Network, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut NeuroMyoGène (INMG), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Charles Foix [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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Chimie, Modélisation et Imagerie pour la Biologie [Orsay], Université Paris-Sud - Paris 11 (UP11)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université - Département de neurologie 2 - Mazarin, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], 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)-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)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche en Cancérologie de Lyon (CRCL), 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), 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), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), and LOMONTE, PATRICK
Subjects: Male, Telomerase, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV]Life Sciences [q-bio], [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], lcsh:RC346-429, MESH: Isocitrate Dehydrogenase, Cohort Studies, 0302 clinical medicine, ATRX loss of expression, Medicine, MESH: Cohort Studies, ComputingMilieux_MISCELLANEOUS, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH: X-linked Nuclear Protein, Brain Neoplasms, MESH: Gene Expression Regulation, Neoplastic, Middle Aged, Isocitrate Dehydrogenase, 3. Good health, Gene Expression Regulation, Neoplastic, Secondary glioblastoma, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Anaplastic astrocytoma, Adult, X-linked Nuclear Protein, IDH1, MESH: Mutation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neuropathology, Astrocytoma, Pathology and Forensic Medicine, MESH: Telomere Homeostasis, 03 medical and health sciences, Cellular and Molecular Neuroscience, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Alternative lengthening of telomeres, Humans, lcsh:Neurology. Diseases of the nervous system, ATRX, Aged, 030304 developmental biology, IDH1/2 mutations, MESH: Humans, business.industry, Research, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Telomere Homeostasis, Cancer, MESH: Adult, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, MESH: Male, Telomere, MESH: Astrocytoma, Mutation, Cancer cell, Cancer research, Neurology (clinical), business, MESH: Female
Abstract: All cancer cells need to maintain functional telomeres to sustain continuous cell division and proliferation. In human diffuse gliomas, functional telomeres are maintained due either to reactivation of telomerase expression, the main pathway in most cancer types, or to activation of a mechanism called the alternative lengthening of telomeres (ALT). The presence of IDH1/2 mutations (IDH-mutant) together with loss of ATRX expression (ATRX-lost) are frequently associated with ALT in diffuse gliomas. However, detection of ALT, anda fortioriits quantification, are rarely, if ever, measured in neuropathology laboratories. We measured the level of ALT activity using the previously described quantitative “C-circle” assay and analyzed it in a well characterized cohort of 104 IDH-mutant and ATRX-lost adult diffuse gliomas. We report that in IDH-mutant ATRX-lost anaplastic astrocytomas, the intensity of ALT was inversely correlated with age (p
Published: 2019

15. Ki‐67 and MCM6 labeling indices are correlated with overall survival in anaplastic oligodendroglioma, IDH1‐mutant and 1p/19q‐codeleted: a multicenter study from the French POLA network

Author: Celso Pouget, Sébastien Hergalant, Emilie Lardenois, Stéphanie Lacomme, Rémi Houlgatte, Catherine Carpentier, Caroline Dehais, Fabien Rech, Luc Taillandier, Marc Sanson, Romain Appay, Carole Colin, Dominique Figarella‐Branger, Shyue‐Fang Battaglia‐Hsu, Guillaume Gauchotte, Christine Desenclos, H. Sevestre, Philippe Menei, A. Rousseau, T. Cruel, S. Lopez, M.I. Mihai, A. Petit, R. Seizeur, I. Quintin‐Roué, C. Adam, F. Parker, S. Eimer, H. Loiseau, L. Bekaert, F. Chapon, D. Ricard, C. Godfraind, T. Khallil, D. Cazals‐Hatem, T. Faillot, C. Gaultier, M. C Tortel, I. Carpiuc, P. Richard, W. Lahiani, H. Aubriot‐Lorton, F. Ghiringhelli, C‐A Maurage, E. Le Rhun, E. M. Gueye, F. Labrousse, F. Ducray, D. Meyronet, O. Chinot, L. Bauchet, V. Rigau, P. Beauchesne, M. Campone, D. Loussouarn, D. Fontaine, F. Vandenbos‐Burel, A. Le. Floch, P. Roger, C. Blechet, M. Fesneau, A. Carpentier, A. Idbaih, J. Y. Delattre, K. Mokhtari, F. Bielle, S. Hamdi, M. Polivka, S. Milin, P. Colin, M. D. Diebold, D. Chiforeanu, E. Vauleon, O. Langlois, A. Laquerriere, F. Forest, M. J. Motso‐Fotso, M. Andraud, G. Runavot, B. Lhermitte, G. Noel, S. Gaillard, C. Villa, N. Desse, C. Rousselot‐Denis, I. Zemmoura, E. Cohen‐Moyal, E. Uro‐Coste, F. Dhermain, Service de Pathologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre de Ressources Biologiques - [Nancy] (CRB Nancy), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurochirurgie [CHRU Nancy], Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de neurologie [CHRU Nancy], OncoNeuroTek [Paris], 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)-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], Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Laboratoire d'Anatomie Pathologique-Neuropathologique [AP-HM Hôpital La Timone], Hôpital de la Timone [CHU - APHM] (TIMONE), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université - Département de neurologie 2 - Mazarin, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), 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)-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]
Subjects: 0301 basic medicine, Male, Proliferation index, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], 0302 clinical medicine, Research Articles, Aged, 80 and over, Brain Neoplasms, General Neuroscience, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Middle Aged, Prognosis, Isocitrate Dehydrogenase, 3. Good health, Survival Rate, Microglial cell activation, Ki-67, Immunohistochemistry, Female, France, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Adult, IDH1, Mitotic index, Oligodendroglioma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Postsynaptic specialization, Pathology and Forensic Medicine, 03 medical and health sciences, Young Adult, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Glioma, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Mitotic Index, Humans, Aged, [INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB], Gene Expression Profiling, medicine.disease, Minichromosome Maintenance Complex Component 6, 030104 developmental biology, Ki-67 Antigen, Mutation, biology.protein, Cancer research, Neurology (clinical), [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], 030217 neurology & neurosurgery, Gene Deletion
Abstract: International audience; Anaplastic oligodendroglioma (AO), IDH‐mutant and 1p/19q codeleted (IDHmut+/1p19qcodel), is a high‐grade glioma with only limited prognostic markers. The primary objective of this study was to evaluate, by immunohistochemistry, the prognostic value of two proliferation markers, MCM6 and Ki‐67, in a large series of IDHmut+/1p19qcodel AO included in the POLA (“Prise en charge des Oligodendrogliomes Anaplasiques”) French national multicenter network. We additionally examined the transcriptome obtained from this series to understand the functional pathways dysregulated with the mRNA overexpression of these two markers. The labelling indices (LI) of MCM6 and Ki‐67 were obtained via computer‐assisted color image analyses on immunostained AO tissues of the cohort (n=220). Furthermore, a subgroup of AO (n=68/220) was used to perform transcriptomic analyses. A high LI of either MCM6 (≥50%) or Ki‐67 (≥ 15%) correlated with shorter overall survival, both in univariate (P=0.013 and P=0.004, respectively) and multivariate analyses (P=0.027; multivariate Cox model including age, mitotic index, MCM6 and Ki‐67). MCM6 and Ki‐67 LI also correlated with overall survival in an additional retrospective cohort of 30 grade II IDHmut+/1p19qcodel oligodendrogliomas. The prognostic value of MCM6 mRNA level was confirmed in The Cancer Genome Atlas (TCGA) IDHmut+/1p19qcodel gliomas. The transcriptomic approach revealed that high transcriptional expressions of MCM6 and MKI67 were both linked positively with cell cycle progression, DNA replication, mitosis, pro‐neural phenotype as well as neurogenesis, and negatively with microglial cell activation, immune response, positive regulation of myelination, oligodendrocyte development, beta‐amyloid binding, and postsynaptic specialization.In conclusion, the overexpression of MCM6 and/or Ki‐67 is independently associated to shorter overall survival in IDHmut+/1p19qcodel AO. These two easy‐to‐use and cost‐effective markers could thus be used concurrently in routine pathology practice. Additionally, the transcriptomic analyses showed that AO with high proliferation index have down‐regulated immune response and lower microglial cells activation, and bears pro‐neural phenotype.
Published: 2019

16. P04.12 Characteristics of IDH-mutant gliomas with non-canonical IDH mutations

Author: C Ferec, Charlotte Bronnimann, Catherine Carpentier, Caroline Dehais, M. Sanson, A Siegfried, D Cappellen, Dominique Figarella-Branger, J.-Y. Delattre, François Ducray, Jean-Sebastien Frenel, S Lacomme, L Poetsch, Delphine Larrieu-Ciron, Sandrine Eimer, Delphine Loussouarn, and Romuald Seizeur
Subjects: Cancer Research, Mutant, Astrocytoma, Cancer, Biology, medicine.disease, nervous system diseases, Poster Presentations, Oncology, Frontal lobe, Non canonical, Glioma, Mutation (genetic algorithm), Cancer research, medicine, Neurology (clinical), Oligodendroglioma, neoplasms
Abstract: BACKGROUND About 10% of IDH-mutant gliomas harbor non-canonical IDH mutations (non-R132H IDH1 and IDH2 mutations). The aim of the present study was to analyze the characteristics of these gliomas in comparison to those of IDH1 R132H mutant gliomas. MATERIAL AND METHODS We retrospectively analyzed the characteristics of a multicentric series of 161 gliomas with non-canonical IDH mutations and compared them to those of consecutive series of 109 IDH1 R132H mutant gliomas. Medical, radiological and pathological were reviewed. RESULTS Median age at diagnosis was 35 years in gliomas with a non-canonical IDH1 mutation, 42 years in those with an IDH2 mutation and 44 years in those with an IDH1R132H mutation. A familial history of cancer was more frequent in gliomas with a non-canonical IDH mutation than in those with an IDH1 R132H mutation (22,3% vs 5,5%, p CONCLUSION Gliomas with non-canonical IDH mutations are associated with distinct clinical, radiological and histological characteristics. Their prognosis, however, is similar to that of gliomas with canonical IDH mutations.
Published: 2019

17. CDKN2A homozygous deletion is a strong adverse prognosis factor in diffuse malignant IDH-mutant gliomas

Author: Jean-Yves Delattre, Ahmed Idbaih, Dominique Figarella-Branger, Caroline Dehais, Fabienne Escande, Emeline Tabouret, Agusti Alentorn, Nesrine Trabelsi, Romain Appay, Claude-Alain Maurage, François Ducray, Karima Mokhtari, Catherine Carpentier, Yannick Marie, Emmanuelle Uro-Coste, Carole Colin, Aurélie Kamoun, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service d’Anatomie Pathologique et de Neuropathologie, APHM, Hôpital de la Timone, Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), 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), biology and pathological laboratory, 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), (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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), Département de neurooncologie, Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Service de Neurologie [CHU Pitié-Salpêtrière], and IFR70-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Male, Cancer Research, Necrosis, [SDV]Life Sciences [q-bio], Cohort Studies, 0302 clinical medicine, CDKN2A, Medicine, ComputingMilieux_MISCELLANEOUS, Sequence Deletion, Aged, 80 and over, Kinase, Retinoblastoma, Brain Neoplasms, Homozygote, Glioma, Middle Aged, Prognosis, Combined Modality Therapy, Isocitrate Dehydrogenase, 3. Good health, Survival Rate, Isocitrate dehydrogenase, Oncology, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Female, medicine.symptom, Adult, Adolescent, 03 medical and health sciences, Young Adult, Biomarkers, Tumor, Humans, Progression-free survival, neoplasms, Cyclin-Dependent Kinase Inhibitor p16, Aged, business.industry, Editorials, medicine.disease, Mutation, Cancer research, Neurology (clinical), business, Chromosomes, Human, Pair 19, 030217 neurology & neurosurgery, Anaplastic astrocytoma, Follow-Up Studies
Abstract: Background The 2016 WHO classification of the central nervous system tumors stratifies IDH-mutant gliomas into two major groups depending on the presence or absence of 1p/19q-codeletion. However, the grading system remains unchanged and it is now controversial whether it can be still applied to this updated molecular classification. Methods In a large cohort of 911 high grade IDH-mutant gliomas from the French national POLA network (including 428 IDH-mutant gliomas without 1p/19q-codeletion and 483 anaplastic oligodendrogliomas, IDH-mutant and 1p/19q-codeleted), we investigated the prognostic value of CDKN2A gene homozygous deletion as well as WHO grading criteria (mitoses, microvascular proliferation and necrosis). In addition, we also searched for other retinoblastoma pathway gene alterations (CDK4 amplification and RB1 homozygous deletion) in a subset of patients. CDKN2A homozygous deletion was also searched in an independent series of 40 grade II IDH-mutant gliomas. Results CDKN2A homozygous deletion was associated with dismal outcome among IDH-mutant gliomas lacking 1p/19q-codeletion (p Conclusions Our study pointed out the utmost relevance of CDKN2A homozygous deletion as an adverse prognostic factor in the two broad categories of IDH-mutant gliomas stratified on 1p/19q-codeletion and suggest to refine the grading of these tumors.
Published: 2019

18. Integrated multi-omics analysis of oligodendroglial tumours identifies three subgroups of 1p/19q co-deleted gliomas

Author: Anne Jouvet, Karima Mokhtari, Marc Sanson, Eric Letouzé, François Ducray, Ahmed Idbaih, Aurélien de Reyniès, Nadine Martin-Duverneuil, Emmanuelle Uro-Coste, Caroline Dehais, Aurélie Kamoun, Dominique Figarella-Branger, Catherine Carpentier, Carole Colin, Jean-Yves Delattre, Nabila Elarouci, (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], 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), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Faculté de Médecine [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), OncoNeuroTek [Paris], 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)-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), Neuro-Oncologie [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), 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), UPMC - Département de neurologie 2 - Mazarin, Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Laboratoire de Neuropathologie Raymond Escourolle, 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Service de Neuroradiologie [CHU Pitié-Salpêtrière], 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)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and HAL UPMC, Gestionnaire
Subjects: Male, 0301 basic medicine, General Physics and Astronomy, Transcriptome, Cluster Analysis, Aged, 80 and over, Neurons, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, Stem Cells, Genomics, Glioma, Middle Aged, 3. Good health, Oligodendroglia, medicine.anatomical_structure, Chromosomes, Human, Pair 1, DNA methylation, Female, Chromosome Deletion, Signal Transduction, Adult, Cell type, Science, Oligodendroglioma, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Proto-Oncogene Proteins c-myc, Young Adult, 03 medical and health sciences, medicine, Humans, Survival analysis, Aged, Gene Expression Profiling, General Chemistry, DNA Methylation, medicine.disease, Survival Analysis, Oligodendrocyte, Gene expression profiling, 030104 developmental biology, Cancer research, Chromosomes, Human, Pair 19, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Oligodendroglial tumours (OT) are a heterogeneous group of gliomas. Three molecular subgroups are currently distinguished on the basis of the IDH mutation and 1p/19q co-deletion. Here we present an integrated analysis of the transcriptome, genome and methylome of 156 OT. Not only does our multi-omics classification match the current classification but also reveals three subgroups within 1p/19q co-deleted tumours, associated with specific expression patterns of nervous system cell types: oligodendrocyte, oligodendrocyte precursor cell (OPC) and neuronal lineage. We confirm the validity of these three subgroups using public datasets. Importantly, the OPC-like group is associated with more aggressive clinical and molecular patterns, including MYC activation. We show that the MYC activation occurs through various alterations, including MYC genomic gain, MAX genomic loss, MYC hypomethylation and microRNA-34b/c down-regulation. In the lower grade glioma TCGA dataset, the OPC-like group is associated with a poorer outcome independently of histological grade. Our study reveals previously unrecognized heterogeneity among 1p/19q co-deleted tumours., Oligodendroglial tumours are characterized into three different molecular subtypes. Here, the authors use genomic data to identify a further three subgroups of 1p/19q co-deleted tumours and demonstrate an association with an aggressive phenotype.
Published: 2016

19. Clinical validation of the CE-IVD marked Therascreen MGMT kit in a cohort of glioblastoma patients

Author: Audrey Lavenu, Dominique Figarella-Branger, Dan Cristian Chiforeanu, Catherine Carpentier, Guenaelle Levallet, Elodie Vauleon, Olivier Chinot, Lucie Karayan-Tapon, David Meyronet, Emmanuèle Lechapt Zalcman, Fabienne Escande, François Ducray, Frédéric Fina, Marc Sanson, Carole Ramirez, Véronique Quillien, Michèle Legrain, Natacha Entz-Werle, Pierre Rivet, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Département de neurooncologie, Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM] (ACPNP), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), 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), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Département d'Oncologie Pédiatrique [CHU Hautepierre, Strasbourg], Hôpital de Hautepierre [Strasbourg], Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Institut Régional du Cancer-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Département de Pathologie [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), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pontchaillou [Rennes], CRLCC Eugène Marquis (CRLCC), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Funding was provided by the French Ministry of Health (Support for Costly Cancer Technical Evaluation – STIC – Gov-0478)., Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie 2 [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Régional du Cancer-Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Centre de Recherche en Cancérologie de Lyon (CRCL), 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)-CHU Pitié-Salpêtrière [APHP], Sorbonne Universités, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], and Jonchère, Laurent
Subjects: Oncology, Male, Cancer Research, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Kaplan-Meier Estimate, In vitro diagnostic, 0302 clinical medicine, MGMT methylation, DNA Modification Methylases, Potential impact, Brain Neoplasms, General Medicine, Methylation, Middle Aged, Prognosis, Grey zone, pyrosequencing, 030220 oncology & carcinogenesis, Cohort, Female, CE-IVD kit, Adult, medicine.medical_specialty, Medical device, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Genetics, Overall survival, medicine, Biomarkers, Tumor, Humans, Genetic Testing, Aged, business.industry, Tumor Suppressor Proteins, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Reproducibility of Results, DNA Methylation, medicine.disease, DNA Repair Enzymes, CpG Islands, Reagent Kits, Diagnostic, business, Glioblastoma, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND: Pyrosequencing is recognized as a strong technique to analyze the MGMT status of glioblastoma patients. The most commonly used assay, quantifies the methylation levels of CpGs 74 to 78. A more recent CE-marked In Vitro Diagnostic Medical Device (CE-IVD) assay, Therascreen, analyzes CpGs 76-79.METHODS: We performed a comparison of these two assays to evaluate the potential impact of this shift in analyzed CpGs. Therascreen analysis was centrally performed for 102 glioblastoma patients, who were part of a prospective multicenter trial.RESULTS: A strong correlation was observed for the mean values of the 4 or 5 analyzed CpGs, with lower values recorded using the Therascreen assay, especially for values greater than 20%. When considering a classification in 3 categories (> 12%: methylated; ⩽ 8%: unmethylated; 9-12%: grey zone), 93% of patients were identically classified between the two assays. Using a binary classification, 95% and 97% of patients were identically classified with cut-offs of 8% and 12%, respectively. A strong prognostic significance was observed for both assays: median overall survival were 15.9 months and 34.9 months for respectively unmethylated and methylated patients with either test. CONCLUSION: The results demonstrate that these assays may be used interchangeably.
Published: 2017

20. Allelic loss of 9p21.3 is a prognostic factor in 1p/19q codeleted anaplastic gliomas

Author: Agustí, Alentorn, Caroline, Dehais, François, Ducray, Catherine, Carpentier, Karima, Mokhtari, Dominique, Figarella-Branger, Olivier, Chinot, Elisabeth, Cohen-Moyal, Carole, Ramirez, Hugues, Loiseau, Selma, Elouahdani-Hamdi, Patrick, Beauchesne, Olivier, Langlois, Christine, Desenclos, Jean-Sébastien, Guillamo, Phong, Dam-Hieu, François, Ghiringhelli, Philippe, Colin, Joel, Godard, Fabrice, Parker, Frédéric, Dhermain, Antoine F, Carpentier, Jean-Sebastien, Frenel, Philippe, Menei, Luc, Bauchet, Thierry, Faillot, Mélanie, Fesneau, Denys, Fontaine, Marie-Jeannette, Motuo-Fotso, Elodie, Vauleon, Claude, Gaultier, Caroline, Le Guerinel, Edouard-Marcel, Gueye, Georges, Noel, Nicolas, Desse, Xavier, Durando, Eduardo, Barrascout, Michel, Wager, Damien, Ricard, Ioana, Carpiuc, Jean-Yves, Delattre, Ahmed, Idbaih, and Chiara, Villa
Subjects: Adult, Male, Oncology, Pathology, medicine.medical_specialty, Multivariate analysis, DNA Copy Number Variations, Loss of Heterozygosity, Single-nucleotide polymorphism, Biology, Article, Loss of heterozygosity, Internal medicine, Glioma, medicine, Humans, Oligodendroglial Tumor, Clinical significance, Prospective Studies, Copy-number variation, Prospective cohort study, Aged, Brain Neoplasms, Middle Aged, Prognosis, medicine.disease, Chromosomes, Human, Pair 1, Female, Neurology (clinical), Chromosome Deletion, Chromosomes, Human, Pair 9
Abstract: Objectives: We aimed to study the potential clinical relevance of 9p allelic loss, with or without copy number variation, in 1p/19q codeleted anaplastic oligodendroglial tumors (AOTs). Methods: This study enrolled 216 patients with 1p/19q codeleted AOT. The prognostic value of 9p allelic loss was investigated using a French nation-wide prospective registry, POLA (prise en charge des tumeurs oligodendrogliales anaplasiques) and high-density single nucleotide polymorphism arrays. We validated our results using the Repository of Molecular Brain Neoplasia Data (REMBRANDT) dataset. Results: The minimal common region of allelic loss in chromosome arm 9p was 9p21.3. Allelic loss of 9p21.3, detected in 41.7% of tumors, was associated with shorter progression-free and overall survival rates in univariate ( p = 0.008 and p p = 0.009 and p = 0.009, respectively). This finding was validated in the REMBRANDT dataset in univariate and multivariate analysis ( p = 0.01 and p = 0.01, respectively). Conclusion: Our study highlights a novel potential prognostic biomarker in 1p/19q codeleted AOT. Further prospective studies are warranted to investigate our finding.
Published: 2015

21. Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis

Author: Gabriel Viennet, Pascale Varlet, Dominique Figarella-Branger, Anh Tuan Nguyen, Clovis Adam, Dominique Cazals-Hatem, Karima Mokhtari, Henri Sevestre, Fabien Forest, François Labrousse, Catherine Carpentier, Sandrine Eimer, Valérie Rigau, Danchristian Chiforeanu, Marie-Hélène Aubriot-Lorton, Carole Colin, Sophie Michalak, F. Vandenbos, Marie-Claire Tortel, Marie-Pierre Chenard, Annie Laquerrière, Isabelle Quintin-Roue, Pomone Richard, Anne Heitzmann, Delphine Loussouarn, Jean Louis Kemeny, Jean-Yves Delattre, Jean-Michel Vignaud, Caroline Dehais, Anne Jouvet, Emmanuelle Uro-Coste, Chiara Villa, Marie-Danièle Diebold, Pierre-Marie Levillain, Marc Polivka, Emmanuelle Lechapt-Zalcman, and Claude-Alain Maurage
Subjects: Pathology, medicine.medical_specialty, IDH1, Necrosis, Direct sequencing, General Neuroscience, Anaplastic oligodendroglioma, IDH1 R132H, Biology, IDH2, nervous system diseases, Pathology and Forensic Medicine, medicine, Neurology (clinical), Progression-free survival, Anaplastic Oligoastrocytoma, medicine.symptom
Abstract: Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO.
Published: 2014

22. OS9.2 Radiomics analysis of lower-grade gliomas, a POLA Network study

Author: Caroline Dehais, L Nichelli, Agusti Alentorn, Nadia Younan, H Douzane, Jean Yves Delattre, Catherine Carpentier, Karima Mokhtari, Ahmed Idbaih, Alberto Duran-Peña, Dominique Figarella-Branger, Y Garcilazo, and François Ducray
Subjects: Cancer Research, medicine.medical_specialty, Lower grade, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, medicine.disease, Stratification (mathematics), Oncology, Radiomics, Frontal lobe, Glioma, Oral Presentations, medicine, Medical imaging, Neurology (clinical), Radiology, Oligodendroglioma, business
Abstract: BACKGROUND Lower-grade gliomas (LGG) are divided into three histo-molecular groups: i) IDH-wildtype, ii) IDH mutant and 1p19q intact and iii) IDH mutant and 1p19q co-deleted. The current classification has improved the clinical stratification and its reproducibility. However, LGGs are still associated with an important degree of clinical heterogeneity. We sought to analyze the cross-talk between the spatial distribution and the quantitative imaging features (radiomics) with the clinical evolution and their molecular background (radiogenomics). MATERIAL AND METHODS We performed a retrospective multicentric study from 4 cohorts of high-grades gliomas (POLA Network, TCGA, REMBRANDT and LGG-1p19q), totaling 900 gliomas. We performed N4 and WhiteStripe imaging corrections to standardize MRI intensities. We used ITK-SNAP to obtain a mask of the different habitats of the tumor. Then we used PyRadiomics to obtain 2616 radiomic features per sample. We used plsRcox for fitting several Cox model in high-dimensional settings. We assessed the performance of the difference Cox model with the Harrel’s concordance index. We used a Sparse Canonical Correlation analysis to analyze the spatial distribution of the tumors. RESULTS Radiomics features allow identification in an unsupervised manner IDH-mutant gliomas with a median AUC of 0.96 [0.92–0.98]. Interestingly, in the analysis of survival, radiomics features provided additional information to clinical or genetics covariates and the model with only radiomics features obtained a C-Index of 0.78 [0.72–0.82]. In addition, survival model with the best performance in the prediction of overall survival was the one combining radiomics, clinics and genetics features with a C-Index 0.85 [0.82–0.92] and was validated in the other cohorts. The analysis of spatial distribution showed a very strong distribution of 1p19q co-deleted oligodendrogliomas in the frontal lobes. CONCLUSION Radiomics features may provide additional relevant clinical information by improving the prognosis of LGG. Radiomics allow non-invasive prediction of the most relevant molecular alterations of LGG.
Published: 2019

23. A gene signature of response to radiotherapy in patients with grade II-III oligodendrogliomas

Author: Julia Gilhodes, Emmanuelle Uro-Coste, Caroline Dehais, Elizabeth Cohen-Jonathan Moyal, Catherine Carpentier, Damien Pouessel, Guillaume Peyraga, François Ducray, and Delphine Larrieu-Ciron
Subjects: Radiation therapy, Cancer Research, Oncology, business.industry, medicine.medical_treatment, medicine, Cancer research, In patient, Oligodendroglioma, medicine.disease, business, Gene, Chromosomal Loss
Abstract: 2041 Background: Grade II and III Oligodendroglioma associate mutations of isocitrate deshydrogenase 1 or 2 genes and the whole-arm chromosomal loss of 1p and 19q and have a better prognosis than other gliomas. However, even if the preferred treatment consists of a combination of radiotherapy (RT) and chemotherapy, some patients will less respond to this treatment and will relapse faster , in part because of an heterogeneity in the response to RT. In the aim to identify factors of response to RT, we analyzed clinical and molecular data of patients with grade II-III oligodendroglioma exclusively treated with RT in the POLA cohort. Methods: Gene expression profiles on Affymetrix expression arrays of patients from the POLA cohort with co-deleted 1p/19q grade II/II gliomas treated by exclusive RT were used to identify a gene expression set predictive of radiation sensitivity. The primary endpoint was the progression free survival (PFS), defined as the time from treatment start until progression or death. A supervised approach with penalized regression was applied to select most informative predictors, and then a risk score was created based on the linear predictor given by the multivariable model. Results: Forty-five patients corresponded to the study criteria, with a median age at diagnosis of 45 (range 23- 64). The supervised approach allowed identifying a three-gene prognostic set including Semaphorin -3C (SEMA3C), Neuronal Pentraxin 2 (NPTX2 ) and the Metabotropic Glutamate Receptor 5 (GRM5), involved in proliferation, migration and inflammation. The risk score associated to these three genes was statistically associated to PFS (HR = 2.72, p = 0.00005) and remains significant when adjusted on clinical covariates age at diagnosis, necrosis, endothelial proliferation and type of surgery (complete, partial or subtotal surgery) (HRadj = 2.36, p = 0.001). Conclusions: We report an independent three genes SEMA3C-NPTX2-GRM5 risk score signature of response to radiotherapy in patients with oligodendroglioma, which highlights the heterogeneous response in this reputed good prognosis population. This signature could help in determining the adapted treatment as well as potential new targets to address.
Published: 2019

24. Le carnet de Laisse ton empreinte. Un outil de reconnaissance mutuelle

Author: Catherine Carpentier
Abstract: Le carnet de Laisse ton empreinte, methodologie particuliere d’entretien, puis d’ecriture du temoignage en vue de remettre a la personne une trace singuliere qui porte son nom et lui appartient modifie le cadre habituel de l’accompagnement quel que soit le champ d’intervention. C’est ce que montre le recit de l’experimentation menee par des travailleurs sociaux aupres de jeunes de la Protection de L’enfance : en quoi donner une autre place au jeune impacte la posture du professionnel, facilite le compagnonnage et la reconnaissance mutuelle.
Published: 2019

25. Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is associated with 9p loss, genomic instability, and angiogenic gene expression

Author: German Reyes-Botero, Caroline Dehais, Ahmed Idbaih, Nadine Martin-Duverneuil, Marion Lahutte, Catherine Carpentier, Eric Letouzé, Olivier Chinot, Hugues Loiseau, Jerome Honnorat, Carole Ramirez, Elisabeth Moyal, Dominique Figarella-Branger, François Ducray, Christine Desenclos, Henri Sevestre, Philippe Menei, Sophie Michalak, Edmond Al Nader, Joel Godard, Gabriel Viennet, Antoine Carpentier, Sandrine Eimer, Phong Dam-Hieu, Isabelle Quintin-Roué, Jean-Sebastien Guillamo, Emmanuelle Lechapt-Zalcman, Jean-Louis Kemeny, Pierre Verrelle, Thierry Faillot, Claude Gaultier, Marie Christine Tortel, Christo Christov, Caroline Le Guerinel, Marie-Hélène Aubriot-Lorton, Francois Ghiringhelli, François Berger, Catherine Lacroix, Fabrice Parker, François Dubois, Claude-Alain Maurage, Edouard-Marcel Gueye, Francois Labrousse, Anne Jouvet, Luc Bauchet, Valérie Rigau, Patrick Beauchesne, Jean-Michel Vignaud, Mario Campone, Delphine Loussouarn, Denys Fontaine, Fanny Vandenbos, Chantal Campello, Pascal Roger, Melanie Fesneau, Anne Heitzmann, Jean-Yves Delattre, Selma Elouadhani, Karima Mokhtari, Marc Polivka, Damien Ricard, Pierre-Marie Levillain, Michel Wager, Philippe Colin, Marie-Danièle Diebold, Dan Chiforeanu, Elodie Vauleon, Olivier Langlois, Annie Laquerriere, Marie Janette Motsuo Fotso, Michel Peoc'h, Marie Andraud, Servane Mouton, Marie-Pierre Chenard, Georges Noel, Nicolas Desse, Raoulin Soulard, Alexandra Amiel-Benouaich, Emmanuelle Uro-Coste, and Frederic Dhermain
Subjects: Adult, Male, Cancer Research, Pathology, medicine.medical_specialty, Oligodendroglioma, Gene Expression, Biology, Polymorphism, Single Nucleotide, Genomic Instability, Young Adult, Gene expression, medicine, Humans, Oligodendroglial Tumor, Aged, Neovascularization, Pathologic, medicine.diagnostic_test, Brain Neoplasms, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Isocitrate Dehydrogenase, Gene expression profiling, Isocitrate dehydrogenase, Oncology, Frontal lobe, Chromosomes, Human, Pair 1, Basic and Translational Investigations, Mutation, Female, Neurology (clinical), Chromosome Deletion, Chromosomes, Human, Pair 9, Chromosomes, Human, Pair 19, SNP array
Abstract: BACKGROUND: The aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs). METHODS: The MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays. RESULTS: Most of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2. CONCLUSION: In AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume.
Published: 2013

26. Validation of the high-performance of pyrosequencing for clinical MGMT testing on a cohort of glioblastoma patients from a prospective dedicated multicentric trial

Author: Véronique Quillien, Olivier Chinot, Dominique Figarella-Branger, Guenaelle Levallet, Michèle Legrain, Marie-Odile Joly, Pierre Rivet, Emmanuèle Lechapt Zalcman, François Ducray, Marc Sanson, Audrey Lavenu, Fabienne Escande, Catherine Carpentier, Natacha Entz-Werle, Lucie Karayan-Tapon, Dan Cristian Chiforeanu, Frédéric Fina, Carole Ramirez, Elodie Vauleon, CRLCC Eugène Marquis (CRLCC), Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hôpital de la Timone [CHU - APHM] (TIMONE), Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), 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)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de Hautepierre [Strasbourg], Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Institut Régional du Cancer-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Département de Pathologie [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), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pontchaillou [Rennes], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)-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), Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [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)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Interlaboratory reproducibility, promoter methylation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Promoter methylation, medicine, Temozolomide, Humans, prospective trial, Prospective Studies, Prospective cohort study, Promoter Regions, Genetic, DNA Modification Methylases, Aged, business.industry, Brain Neoplasms, Tumor Suppressor Proteins, glioblastoma, Reproducibility of Results, Sequence Analysis, DNA, DNA Methylation, Middle Aged, medicine.disease, 3. Good health, Surgery, First line treatment, Dacarbazine, DNA Repair Enzymes, pyrosequencing, 030220 oncology & carcinogenesis, Cohort, Pyrosequencing, Female, business, MGMT, 030217 neurology & neurosurgery, medicine.drug, Glioblastoma, Research Paper
Abstract: International audience; Background: The goal of this prospective multicentric trial was to validate a technique that allowed for MGMT promoter methylation analysis in routine clinical practice.Methods: The MGMT status of 139 glioblastoma patients, whom had received standard first line treatment, was determined using pyrosequencing (PSQ) and a semi-quantitative Methylation-specific PCR (sqMS-PCR) method, using both frozen and formalin-fixed paraffin-embedded FFPE samples. Eight participating centers locally performed the analysis, including external quality controls.Results: There was a strong correlation between results from FFPE and frozen samples. With cut-offs of 12% and 13%, 98% and 91% of samples were identically classified with PSQ and sqMS-PCR respectively. In 12% of cases frozen samples were excluded because they had a low percentage of tumor cells. In 5-6% of cases the analysis was not feasible on FFPE samples. The optimized risk cut-offs were higher in both techniques when using FFPE samples, in comparison to frozen samples. For sqMS-PCR, we validated a cut-off between 13-15% to dichotomize patients. For PSQ, patients with a low level of methylation (
Published: 2016

27. Tumor cells with neuronal intermediate progenitor features define a subgroup of 1p/19q co-deleted anaplastic gliomas

Author: Franck, Bielle, François, Ducray, Karima, Mokhtari, Caroline, Dehais, Homa, Adle-Biassette, Catherine, Carpentier, Anaïs, Chanut, Marc, Polivka, Sylvie, Poggioli, Shai, Rosenberg, Marine, Giry, Yannick, Marie, Charles, Duyckaerts, Marc, Sanson, Dominique, Figarella-Branger, Ahmed, Idbaih, and Frédéric, Dhermain
Subjects: Adult, Male, Brain Neoplasms, Neurogenesis, Oligodendroglioma, Computational Biology, SOX9 Transcription Factor, Middle Aged, Repressor Proteins, Phenotype, Neural Stem Cells, Chromosomes, Human, Pair 1, Humans, Female, Chromosome Deletion, Chromosomes, Human, Pair 19, Research Articles, Retrospective Studies
Abstract: The integrated diagnosis of anaplastic oligodendroglioma, IDH mutant and 1p/19q co‐deleted, grade III (O3(id)) is a histomolecular entity that WHO 2016 classification distinguished from other diffuse gliomas by specific molecular alterations. In contrast, its cell portrait is less well known. The present study is focused on intertumor and intratumor, cell lineage‐oriented, heterogeneity in O3(id). Based on pathological, transcriptomic and immunophenotypic studies, a novel subgroup of newly diagnosed O3(id) overexpressing neuronal intermediate progenitor (NIP) genes was identified. This NIP overexpression pattern in O3(id) is associated with: (i) morphological and immunohistochemical similarities with embryonic subventricular zone, (ii) proliferating tumor cell subpopulation with NIP features including expression of INSM1 and no expression of SOX9, (iii) mutations in critical genes involved in NIP biology and, (iv) increased tumor necrosis. Interestingly, NIP tumor cell subpopulation increases in O3(id) recurrence compared with paired newly diagnosed tumors. Our results, validated in an independent cohort, emphasize intertumor and intratumor heterogeneity in O3(id) and identified a tumor cell subpopulation exhibiting NIP characteristics that is potentially critical in oncogenesis of O3(id). A better understanding of spatial and temporal intratumor cell heterogeneity in O3(id) will open new therapeutic avenues overcoming resistance to current antitumor treatments.
Published: 2016

28. Prognostic impact of the 2016 WHO classification of diffuse gliomas in the French POLA cohort

Author: Dominique Figarella-Branger, Anh Tuan Nguyen, Hugues Loiseau, Jean-Yves Delattre, Claude-Alain Maurage, Olivier Chinot, François Ducray, Carole Colin, Ahmed Idbaih, Elisabeth Moyal, Emmanuelle Uro-Coste, Emmanuèle Lechapt-Zalcman, Caroline Dehais, Catherine Carpentier, Christine Desenclos, Emeline Tabouret, Karima Mokhtari, Anne Jouvet, David Meyronet, Marc Polivka, Neuro-Oncologie [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM] (ACPNP), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pitié-Salpêtrière [APHP], 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 [APHP]-Centre National de la Recherche Scientifique (CNRS), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), 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), Laboratoire de Neuropathologie Raymond Escourolle, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud, CHU Toulouse [Toulouse], Faculté de Médecine [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], CHU de Bordeaux Pellegrin [Bordeaux], Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pathologie, AP-HP Hôpital Lariboisière [Paris], Laboratoire d'Anatomie Pathologique [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), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de neurochirurgie, Hôpital Nord - Amiens, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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)-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), 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)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Pathology, IDH1, Adolescent, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Oligodendroglioma, [SDV.CAN]Life Sciences [q-bio]/Cancer, 1p/19q Codeletion, Astrocytoma, World Health Organization, Disease-Free Survival, Pathology and Forensic Medicine, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, 0302 clinical medicine, Internal medicine, medicine, Humans, Oligodendroglial Tumor, neoplasms, Pathological, Grading (tumors), Aged, Aged, 80 and over, business.industry, Brain Neoplasms, Glioma, Middle Aged, medicine.disease, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Mutation, Female, Neurology (clinical), Who classification, business, 030217 neurology & neurosurgery, Anaplastic astrocytoma
Abstract: The new WHO classification of diffuse gliomas has been refined and now includes the 1p/19q codeletion, IDH1/2 mutation, and histone H3-K27M mutation. Our objective was to assess the prognostic value of the updated 2016 WHO classification in the French POLA cohort. All cases of high-grade oligodendroglial tumors sent for central pathological review and included into the French nationwide POLA cohort were reclassified according to the updated 4th WHO classification. In total, 1041 patients were included, with a median age at diagnosis of 50.4 years (range 17.1–84.4). Based on the new histomolecular classification, diagnoses included anaplastic oligodendroglioma IDH mutant and 1p/19q-codeleted (32.5 %), anaplastic astrocytoma IDH mutant (IDH mut) (11.0 %), anaplastic astrocytoma IDH wild type (IDH wt) (5.3 %), glioblastoma IDH mut (17.1 %), and glioblastoma IDH wt (33.2 %). Ten patients presented with a diffuse midline tumor, H3 K27M mutant. The new WHO classification was prognostic for progression-free survival (PFS) and overall survival (OS) (p
Published: 2016

29. Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951

Author: Cyril Dalmasso, Johannes L. Teepen, Johan M. Kros, Philippe Broët, Olivier Delattre, Martin J. van den Bent, Thierry Gorlia, Karima Mokhtari, Catherine Carpentier, Khê Hoang-Xuan, Jean-Yves Delattre, Judith W. M. Jeuken, Ahmed Idbaih, Mathilde C.M. Kouwenhoven, Pim J. French, M. Sanson, Neurology, and Pathology
Subjects: Oncology, Male, Cancer Research, Pathology, Chromosomes, Artificial, Bacterial, medicine.medical_treatment, BAC-array based comparative genomic hybridization (aCGH), Kaplan-Meier Estimate, Anaplastic Oligodendroglioma, Lomustine, Antineoplastic Combined Chemotherapy Protocols, Multicenter Studies as Topic, Oligodendroglial Tumor, In Situ Hybridization, Fluorescence, Comparative Genomic Hybridization, Brain Neoplasms, Laboratory Investigation - Human/Animal Tissue, Middle Aged, Prognosis, Phenotype, Combined Modality Therapy, Treatment Outcome, Neurology, Vincristine, Biomarker (medicine), Adult, medicine.medical_specialty, Oligodendroglioma, Clinical Neurology, Biology, Chromosome, Young Adult, Translational research [ONCOL 3], Internal medicine, medicine, Biomarkers, Tumor, Humans, Aged, Proportional Hazards Models, Retrospective Studies, Chromosome Aberrations, Radiotherapy, Proportional hazards model, medicine.disease, Radiation therapy, Fluorescent in situ hybridization (FISH), Procarbazine, Neurology (clinical), Comparative genomic hybridization
Abstract: Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify new genomic regions associated with prognosis, 60 AOTs from the EORTC trial 26951 were analyzed retrospectively using BAC-array-based comparative genomic hybridization. The data were processed using a binary tree method. Thirty-three BACs with prognostic value were identified distinguishing four genomic subgroups of AOTs with different prognosis (p
Published: 2011

30. Améliorer la prise en charge des cancers rares du cerveau avec le réseau POLA

Author: Robert Terziev, Mylène Ravin, Catherine Carpentier, Marie-Dominique Cantal-Dupart, and Caroline Dehais
Subjects: General Nursing
Published: 2014

31. P01.148 Intra-tumor heterogeneity analysis of low-grade gliomas. A POLA Network study

Author: Marc Sanson, François Ducray, Jean Yves Delattre, Karima Mokhtari, Catherine Carpentier, A. Idbaih, Dominique Figarella-Branger, Agusti Alentorn, Karim Labreche, and Caroline Dehais
Subjects: Poster Presentations, Oncology, Cancer Research, medicine.medical_specialty, Genetic heterogeneity, Internal medicine, Glioma, medicine, Low-Grade Glioma, Neurology (clinical), medicine.disease, Tumor heterogeneity
Abstract: BACKGROUND: Low-grade gliomas (LGG) are divided into three histo-molecular groups: i) IDHwt, ii) IDHmut and 1p19q intact and iii) 1p19q co-deleted with IDH1 mutation. The current classification has improved the clinical stratification and its reproducibility. However, LGGs are still associated with an important degree of clinical heterogeneity.We sough to analyze the genomic and genetic heterogeneity by re-analyzing next-generation sequencing data of two different cohorts of LGG to dissect the potential role of clonal architecture on the clinical evolution of LGG. MATERIAL AND METHODS: We have re-analyzed whole-exome sequencing (WES) using LGG TCGA dataset and a cohort of 40 LGG analyzed by WES from the POLA Network. We have obtained the clonal architecture, the mutation burden, the number of clones, the clonal and subclonal distribution of genetic and genomic alterations and the distribution of the somatic signatures. In addition, we have also analyzed 5 1p19q co-deleted samples at different timepoints to further dissect the clonal evolution of this entity. RESULTS: As expected, the mutation burden of LGG is low (median somatic mutation per sample 34). Surprisingly, the number the subclones was higher in the 1p19q co-deleted subgroup.LGG were enriched in somatic signatures associated with hydrolytic deamination of methylated CpG and with deficiency of mismatch repair. Interestingly, only within 1p19q co-deleted gliomas, the number of subclones, the mutant-allele tumor heterogeneity (MATH) score and the signature associated with hydrolytic deamination of methylated CpGwere associated with poorer outcome in univariate analysis. Finally, only the enrichment of the mutational signature associated with hydrolytic deamination of methylated CpG had prognostic impact in 1p19q co-deleted LGG in Cox multivariate analysis afteradjusting by age, mutational clones number, MATH score and loss of CDKN2A loss. CONCLUSION: The clonal architecture of LGG may provide additional clinical relevant data within 1p19q co-deleted tumors. The enrichment of a somatic signature associated with hydrolytic deamination of methylated CpG is independently associated with poor overall survival.
Published: 2018

32. Up-front temozolomide in elderly patients with anaplastic oligodendroglioma and oligoastrocytoma

Author: Monica Sierra del Rio, Sophie Taillibert, François Ducray, Marc Sanson, Dimitri Psimaras, Gentian Kaloshi, Ahmed Idbaih, Caroline Dehais, Khê Hoang-Xuan, Jean-Yves Delattre, Karima Mokhtari, Antonio Omuro, Florence Laigle-Donadey, and Catherine Carpentier
Subjects: Male, Cancer Research, medicine.medical_specialty, Oligoastrocytoma, medicine.medical_treatment, Oligodendroglioma, Polymerase Chain Reaction, Gastroenterology, Stable Disease, Internal medicine, Temozolomide, medicine, Humans, Promoter Regions, Genetic, Antineoplastic Agents, Alkylating, DNA Modification Methylases, Aged, Retrospective Studies, Aged, 80 and over, Chemotherapy, Brain Neoplasms, business.industry, Tumor Suppressor Proteins, Retrospective cohort study, DNA, Neoplasm, DNA Methylation, medicine.disease, Surgery, Dacarbazine, Survival Rate, Radiation therapy, DNA Repair Enzymes, Treatment Outcome, Neurology, Oncology, Tumor progression, Female, Neurology (clinical), business, Follow-Up Studies, medicine.drug
Abstract: Optimal treatment of anaplastic oligodendrog- lial tumors (AOT) in elderly patients is debatable. We report a retrospective study of 44 consecutive patients aged 70 years or older (median age: 74 years; median Karnofsky performance status (KPS): 70) treated with up-front che- motherapy using temozolomide (TMZ) at conventional doses until tumor progression. O 6 -methylguanine-DNA methyltransferase promoter (MGMTP) methylation was assessed in 38 patients. Of the 41 evaluable patients, partial response (PR) was seen in 13 (32%) patients, 17 (41%) patients achieved stable disease, while the disease pro- gressed in 11 (27%) patients. Median progression-free survival (PFS) and overall survival (OS) were 6.9 and 12.4 months, respectively. Hematoxicity grades 3-4 occurred in nine patients (20%). MGMTP was methylated in 50% of patients and was associated with both longer PFS (8.7 versus 5.7 months, P = 0.01) and longer OS (16.1 versus 12.4 months, P = 0.05). The rate of responders to chemotherapy was similar in MGMTP-methylated (38%) and in MGMTP-unmethylated patients (31%), but duration of response was significantly longer in responders with methylated MGMTP than in responders with unmethylated MGMTP (16.1 versus 9.6 months, P = 0.0004). This study demonstrates that a substantial number of elderly patients with AOT can achieve prolonged survival with up-front chemotherapy using TMZ. Further investigation is needed to determine whether this treatment is preferable to initial radiation therapy.
Published: 2010

33. All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2

Author: C. Falet, Marianne Labussière, Julien Laffaire, J.-Y. Delattre, Emmanuelle Crinière, Ahmed Idbaih, Karima Mokhtari, Catherine Carpentier, Marc Sanson, Blandine Boisselier, Y. Marie, X Wang, S. El Hallani, François Ducray, Khê Hoang-Xuan, and Sophie Paris
Subjects: Genetics, Mutation rate, Mutation, IDH1, Brain Neoplasms, Glioma, 1p/19q Codeletion, Biology, medicine.disease_cause, medicine.disease, Survival Analysis, IDH2, Isocitrate Dehydrogenase, Isocitrate dehydrogenase, Chromosomes, Human, Pair 1, Cancer research, medicine, Humans, Neurology (clinical), Carcinogenesis, Follow-Up Studies, Genome-Wide Association Study
Abstract: Background: Recently, the gene encoding the human cytosolic NADPH-dependent isocitrate dehydrogenase ( IDH1 ) was reported frequently mutated in gliomas. Rare mutations were also found in the sequence of the mitochondrial isoform IDH2 . Methods: In a series of 764 gliomas genome-wide characterized, we determined the presence of mutations in the sequences of both IDH1 and IDH2 genes by direct sequencing. Results: We found that all tumors with complete 1p19q codeletion (n = 128) were mutated in the IDH1 (118) or IDH2 (10) gene. This 100% mutation rate contrasted strikingly with other gliomas exhibiting either variable 1p and 19q alterations (n = 159, IDH1/IDH2 mutation rate of 33%) or no 1p19q alteration (n = 477, IDH1/IDH2 mutation rate 32%). Our data also confirm the prognostic impact of IDH1/IDH2 mutation in gliomas whatever grade considered: patients harboring mutations of IDH1/IDH2 have an improved median overall survival. Moreover, in WHO grade II and III gliomas, 3 groups with significantly different outcomes were identified according to their 1p19q and IDH1/IDH2 statuses. Tumors carrying both alterations had longer overall survival than their nonmutated counterpart. Conclusions: This exclusive association suggests a new mechanism of tumorigenesis. Perhaps the IDH1/IDH2 mutation is a prerequisite for the occurrence of the t(1;19) translocation, or it is required for the 1p19q codeleted cells to acquire a tumor phenotype.
Published: 2010

34. Bevacizumab and irinotecan for recurrent oligodendroglial tumors

Author: Dimitri Psimaras, Caroline Dehais, M. Sanson, Catherine Carpentier, Rémy Guillevin, J.-Y. Delattre, L. A. Vincent, Karima Mokhtari, Florence Laigle-Donadey, A. Bellanger, Audrey Rousseau, B. Granger, S. Taillibert, M. Sierra Del Rio, Y. Meng, Y. Marie, and Khê Hoang-Xuan
Subjects: Adult, Male, medicine.medical_specialty, Bevacizumab, medicine.medical_treatment, DNA Mutational Analysis, Oligodendroglioma, Angiogenesis Inhibitors, Antibodies, Monoclonal, Humanized, Irinotecan, Gastroenterology, Young Adult, Median follow-up, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Oligodendroglial Tumor, Genetic Testing, Survival rate, Aged, Cerebral Hemorrhage, Retrospective Studies, Chemotherapy, Temozolomide, Brain Neoplasms, business.industry, Antibodies, Monoclonal, Middle Aged, Antineoplastic Agents, Phytogenic, Surgery, Survival Rate, Regimen, Treatment Outcome, Patient Compliance, Camptothecin, Female, Neurology (clinical), Neoplasm Recurrence, Local, business, medicine.drug
Abstract: Background: Treatment with a regimen of bevacizumab–irinotecan has been shown to be effective in recurrent grade 3 and 4 gliomas, but the effect of this regimen against recurrent oligodendroglial tumors has not been specifically studied. Methods: The bevacizumab–irinotecan regimen was retrospectively evaluated in a consecutive series of 25 patients with recurrent oligodendroglial tumors. All patients had not responded to previous treatment with radiation therapy and at least one line of temozolomide chemotherapy. Bevacizumab (10 mg/kg) and irinotecan (125 or 340 mg/m 2 according to the antiepileptic regimen) were administered every 14 days. Response was measured clinically and on monthly MRI. Results: The objective response rate was 72% (20% complete response, 52% partial response). After a median follow up of 202 days, the median progression-free survival was 140 days (95% confidence interval [CI] 116–∞), and overall survival had not been reached. The 6-month progression-free survival was 42% (95% CI 26%–67%). Among the 17 patients in whom the status of the main molecular alterations of gliomas could be evaluated (search for deletions of chromosomes 1p, 19q, 9p, and 10q and amplification of epidermal growth factor receptor, mouse double-minute gene, and cyclin-dependent kinase 4 gene), no relation could be found between the response rate and the type of genetic change (including 1p-19q codeletion). The profile of tolerance was fair, with treatment discontinuation in 20% of patients. Intratumoral hemorrhages occurred in 6 patients (24%), but the treatment had to be discontinued because of symptomatic bleeding in only 1 patient (4%). Conclusions: This regimen is effective in recurrent oligodendrogliomas, and the overall tolerance is acceptable.
Published: 2009

35. Chromosome 1p loss evaluation in anaplastic oligodendrogliomas

Author: Judith W. M. Jeuken, Pim J. French, Catherine Carpentier, Khê Hoang-Xuan, Jean-Yves Delattre, Ahmed Idbaih, Olivier Delattre, Johannes L. Teepen, Johan M. Kros, Thierry Gorlia, Mathilde C.M. Kouwenhoven, Martin J. van den Bent, Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Department of Neurology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Pathology, Radboud University Medical Center [Nijmegen], EORTC, European Organization for Research and Treatment of Cancer DataCenter, St. Elisabeth Hospital, 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), UPMC - Département de neurologie 2 - Mazarin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Erasmus University Medical Center [Rotterdam], 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 ), Département de neurologie 2 - Mazarin, CHU Pitié-Salpêtrière [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP)-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Neurology, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, CCA - Cancer Treatment and quality of life, Idbaih, Ahmed, 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)-Sorbonne Université (SU)-Sorbonne Université (SU), Pathology, and Neurosurgery
Subjects: Chromosomes, Artificial, Bacterial, MESH : Oligodendroglioma, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH : Chromosomes, Human, Pair 1, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Nucleic Acid Hybridization, 0302 clinical medicine, MESH : Tumor Markers, Biological, Oligodendroglial Tumor, MESH: In Situ Hybridization, Fluorescence, In Situ Hybridization, Fluorescence, Molecular diagnosis, prognosis and monitoring [UMCN 1.2], Genetics, MESH: Middle Aged, Brain Neoplasms, Nucleic Acid Hybridization, General Medicine, Middle Aged, MESH : Nucleic Acid Hybridization, MESH : In Situ Hybridization, Fluorescence, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, Biomarker (medicine), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Chromosome Deletion, MESH : Chromosomes, Artificial, Bacterial, MESH: Chromosomes, Artificial, Bacterial, MESH: Chromosomes, Human, Pair 1, MESH: Chromosome Deletion, Oligodendroglioma, Anaplastic oligodendroglioma, [SDV.CAN]Life Sciences [q-bio]/Cancer, In situ hybridization, Biology, Pathology and Forensic Medicine, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Translational research [ONCOL 3], medicine, Biomarkers, Tumor, Humans, MESH : Middle Aged, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Brain Neoplasms, MESH: Oligodendroglioma, Bacterial artificial chromosome, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH : Humans, Chromosome, medicine.disease, MESH : Chromosome Deletion, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Tumor Markers, Biological, Neurology (clinical), [ SDV.GEN ] Life Sciences [q-bio]/Genetics, 030217 neurology & neurosurgery, Comparative genomic hybridization
Abstract: Contains fulltext : 69651.pdf (Publisher’s version ) (Closed access) The chromosome (chr) 1p deletion is a favorable biomarker in oligodendroglial tumors and is even more powerful a marker when combined with chr 19q loss. As a result, the 1p deletion is taken into account more and more in clinical trials and the management of patients. However, the laboratory technique implemented for detection of this biomarker has been a topic of debate. To illustrate the usefulness of evaluating multiple loci, we here report two anaplastic oligodendrogliomas that were investigated using fluorescent in situ hybridization (FISH) and bacterial artificial chromosome (BAC)-array-based comparative genomic hybridization (aCGH). Indeed, segmental analysis using FISH, limited to chr 1p36 was unable to discriminate between complete and partial deletions of chrs 1p. However, complete and partial deletions of 1p are reported to have distinct clinical outcomes. Our results illustrate that aCGH (or other multiple loci technologies) provide complementary information to single locus technologies such as FISH because multiple loci technologies can evaluate the extent of the chr 1p deletion.
Published: 2008

36. La promotion des firmes françaises de biotechnologie

Author: Valérie Revest, Isabelle Liotard, Catherine Carpentier, Centre d'Economie de l'Université Paris Nord (CEPN), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Centre National de la Recherche Scientifique (CNRS), and Revest, Valérie
Subjects: financement, Economics and Econometrics, patents, petites entreprises, biotechnologie, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, financing, Industrial relations, brevets, institutions, [SHS.ECO] Humanities and Social Sciences/Economics and Finance, small firms, authorities, Biotechnology, Patents, Financing, Innovating firms, pouvoirs publics, biotechnology
Abstract: L'objectif de cet article est d'étudier le système de promotion des entreprises françaises de biotechnologie. L'exemple des Etats-Unis où l'industrie des biotechnologies a émergé dans les années quatre-vingt constitue notre point de départ. Nous nous focalisons plus particulièrement sur deux facteurs institutionnels qui ont contribué au succès des biotechnologies américaines : les systèmes de propriété intellectuelle et de financement. Nous examinons la manière dont ces facteurs contribuent au développement des entreprises françaises. Ce travail s'appuie sur les résultats d'une étude empirique conduite auprès de petites entreprises innovantes créées entre 1985 et 2005.
Published: 2007

37. FABP7 expression in glioblastomas: relation to prognosis, invasion and EGFR status

Author: Catherine Carpentier, Sophie Taillibert, Karima Mokhtari, Marc Sanson, Gentian Kaloshi, Julie Lejeune, Yannick Marie, Jean-Yves Delattre, and Roseline Godbout
Subjects: Adult, Male, Cytoplasm, Cancer Research, Pathology, medicine.medical_specialty, Poor prognosis, EGFR Amplification, Kaplan-Meier Estimate, Biology, Gene duplication, Biomarkers, Tumor, medicine, Humans, Neoplasm Invasiveness, Aged, Cell Nucleus, Brain Neoplasms, Tumor Suppressor Proteins, Gene Amplification, Histology, Middle Aged, FABP7, Prognosis, medicine.disease, Nuclear translocation, ErbB Receptors, Protein Transport, Cell nucleus, medicine.anatomical_structure, Neurology, Oncology, Female, Neurology (clinical), Carrier Proteins, Fatty Acid-Binding Protein 7, Glioblastoma
Abstract: FABP7 expression has been analysed in a series of 123 glioblastomas (68 pure GBM, 55 GBMO, i.e. with oligodendroglial component). FABP7, found in 91/123 samples, showed a pure cytoplasmic expression in 69 cases, and cytoplasmic + nuclear expression in 22 cases. FABP7 expression was associated with pure GBM histology and shorter survival (15.7 months versus 21.5 months). Nuclear expression of FABP7 was more specifically related to EGFR amplification and more invasive tumors. These data, although they need to be confirmed by further studies, support the relation between FABP7, astrocytic features, invasion and poor prognosis and suggests that EGFR amplification is associated with nuclear translocation of FABP7.
Published: 2007

38. Dramatic response of a BRAF V600E-mutated primary CNS histiocytic sarcoma to vemurafenib

Author: Simon de Bernard, Neila Benameur, Nadine Martin-Duverneuil, Vlad-Ciprian Barlog, Jean Donadieu, Khê Hoang-Xuan, Jean-François Emile, Hayat Belaid, Loïc Feuvret, Damien Galanaud, Catherine Carpentier, Dimitri Psimaras, Jean-Yves Delattre, Noël Zahr, Julien Haroche, Ahmed Idbaih, Karima Mokhtari, 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)-Centre National de la Recherche Scientifique (CNRS)-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 de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Service de Neuroradiologie [CHU Pitié-Salpêtrière], Laboratory of Physics of Materials and Nanomaterials Applied at Environment (LaPhyMNE), Université de Gabès, CHU Trousseau [APHP], 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), 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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (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)-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)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Adult, Male, Proto-Oncogene Proteins B-raf, Indoles, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Treatment outcome, Antineoplastic Agents, Histiocytic sarcoma, Central Nervous System Neoplasms, Fatal Outcome, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Macrophage, Humans, Point Mutation, Vemurafenib, Histiocyte, ComputingMilieux_MISCELLANEOUS, Sulfonamides, business.industry, Monocyte, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], medicine.disease, Magnetic Resonance Imaging, 3. Good health, BRAF V600E, medicine.anatomical_structure, Treatment Outcome, Histiocytoses, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Cancer research, Neurology (clinical), Histiocytic Sarcoma, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, medicine.drug
Abstract: Histiocytic sarcoma (HS) is classified within the malignant histiocytic disorders.1 Involvement of isolated CNS in HS, termed primary CNS-HS (PCNS-HS), is characterized by a proliferation of cells in the monocyte/macrophage lineage within the CNS.2–6 This case report documents the clinical, biological, pathologic, and radiologic spectrums of PCNS-HS. Acknowledgment: The authors thank Groupe Francais d’Etude des Histiocytoses and Dr. Frederic Charlotte for help with the pathologic review.
Published: 2014

39. Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations

Author: Dominique, Figarella-Branger, Karima, Mokhtari, Caroline, Dehais, Anne, Jouvet, Emmanuelle, Uro-Coste, Carole, Colin, Catherine, Carpentier, Fabien, Forest, Claude-Alain, Maurage, Jean-Michel, Vignaud, Marc, Polivka, Emmanuelle, Lechapt-Zalcman, Sandrine, Eimer, Gabriel, Viennet, Isabelle, Quintin-Roué, Marie-Hélène, Aubriot-Lorton, Marie-Danièle, Diebold, Delphine, Loussouarn, Catherine, Lacroix, Valérie, Rigau, Annie, Laquerrière, Fanny, Vandenbos, Sophie, Michalak, Henri, Sevestre, Michel, Peoch, François, Labrousse, Christo, Christov, Jean-Louis, Kemeny, Marie-Pierre, Chenard, Danchristian, Chiforeanu, François, Ducray, Ahmed, Idbaih, Frederic, Dhermain, Laboratoire d'anatomie pathologique - [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-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), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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), Centre de Pathologie et de Neuropathologie Est, Hospices Civils de Lyon (HCL), Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSERM, U975, Université Paris 06, Service d’Anatomie et Cytologie Pathologiques, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service d'Anatomie Pathologique, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d’Anatomie Pathologique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'anatomie et cytologie pathologiques, 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), Laboratoire d'Anatomie Pathologique [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), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Pathologie-Neuropathologie, CHU de Bordeaux Pellegrin [Bordeaux], Histologie et Pathologie Moléculaire, Université Bordeaux Segalen - Bordeaux 2, Service Anatomie et Cytologie Pathologiques, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHRU Brest - Laboratoire d'Anatomo-Pathologie (CHU - AnaPath), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'anatomie et cytologie pathologiques [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Anatomie Pathologique B, Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Anatomie et Cytologie Pathologique, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire d'Anatomie et Cytologie Pathologiques, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), chu de nice, Hôpital Pasteur, Laboratoire Central d’Anatomo Pathologie, Hôpital Pasteur [Nice] (CHU), Département de pathologie cellulaire et tissulaire, CHU d'Angers, 4, rue Larrey, 49100 Angers, France., Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'Anatomie et Cytologie Pathologiques, CHU Amiens-Picardie, Service d'Anatomie Pathologique [CHU Limoges], CHU Limoges, Hôpital Henri Mondor, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire d'anatomie pathologique - Hôpital de Hautepierre Hôpitaux Universitaires de Strasbourg - Université de Strasbourg, Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Service de neuro-oncologie [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neuropathologie Raymond Escourolle [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], 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 neurologie 2 [CHU Pitié-Salpêtrière], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Etienne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service d'Anatomie et Cytologie Pathologique [Rouen], AP-HP Hôpital Henri Mondor (Créteil), 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], Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de Neuropathologie [CHU Pitié Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Nord [CHU - APHM]-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Centre National de la Recherche Scientifique (CNRS)-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), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université
Subjects: Cancer Research, Pathology, medicine.medical_specialty, IDH1, Necrosis, Mitotic index, Proliferation index, [SDV]Life Sciences [q-bio], Oligodendroglioma, Biology, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Chromosome instability, medicine, Mitotic Index, Humans, Progression-free survival, ComputingMilieux_MISCELLANEOUS, Neovascularization, Pathologic, Brain Neoplasms, Brain, medicine.disease, Isocitrate Dehydrogenase, 3. Good health, Oncology, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Basic and Translational Investigations, Chromosome abnormality, Neurology (clinical), medicine.symptom, Chromosome Deletion, Chromosomes, Human, Pair 19, 030217 neurology & neurosurgery
Abstract: BACKGROUND: The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AO). METHODS: The histological characteristics of 203 AO patients enrolled in the French national network POLA were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing. RESULTS: 1p/19q co-deletion was present in 79% of cases and was associated with alpha-internexin expression (p < 10-4), IDH1/2 mutation (p < 10-4), chromosome 4 loss (p < 10-3), and better overall survival (p < 10-4). Based on mitotic index, microvascular proliferation (MVP) and necrosis, 3 groups of 1p/19q co-deleted AO were identified: AO with more than 5 mitoses per 10-HPF, no MVP and no necrosis, (1), AO with MVP and no necrosis (2) and AO with MVP and necrosis (3). Compared to group 1, group 2 and 3 AO had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared to group 2, group 3 AO had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q co-deleted AO, chromosomal instability was associated with shorter progression free survival (p = 0.024) and shorter overall survival (p = 0.023). CONCLUSIONS: The present study shows that oligodendroglioma with classic histological features remains a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q co-deleted AO are also heterogeneous. Interestingly, mitotic index, MVP and necrosis help to classify them into three groups associated with distinct genomic alterations.
Published: 2014

40. [Improving the management of rare brain cancers with the POLA network]

Author: Robert, Terziev, Mylène, Ravin, Catherine, Carpentier, and Caroline, Dehais
Subjects: Biomedical Research, Brain Neoplasms, Humans, Glioma, Community Networks, Quality Improvement
Abstract: The national POLA network is dedicated to the management of certain rare brain tumours, mainly anaplastic oligodendrogliomas, anaplastic oligoastrocytomas and glioblastomas with oligodendroglioma component. The nursing team and the patient are at the heart of the organisation.
Published: 2014

41. Clinical value of chromosome arms 19q and 11p losses in low-grade gliomas

Author: Pieter Wesseling, Ahmed Idbaih, Ilari Scheinin, Blandine Boisselier, Jean-Yves Delattre, Laurent Capelle, Bauke Ylstra, Hussa Alshehhi, Khê Hoang-Xuan, Marc Sanson, Agusti Alentorn, Hinke F. van Thuijl, Karima Mokhtari, Jaap C. Reijneveld, Catherine Carpentier, Florence Laigle-Donadey, Yannick Marie, Neurology, Pathology, and CCA - Disease profiling
Subjects: Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Biology, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Bioinformatics, Glioma, Internal medicine, medicine, Humans, Prospective cohort study, Survival analysis, Brain Neoplasms, Chromosomes, Human, Pair 11, Astrocytoma, O-6-methylguanine-DNA methyltransferase, Methylation, Middle Aged, medicine.disease, Phenotype, Survival Analysis, Chromosomes, Human, Pair 1, Basic and Translational Investigations, Biomarker (medicine), Female, Neurology (clinical), Chromosome Deletion, Glioblastoma, Chromosomes, Human, Pair 19
Abstract: Item does not contain fulltext BACKGROUND: Diffuse low-grade gliomas (LGGs) form a heterogeneous subgroup of gliomas in adults. Chromosome (chr) arms 1p/19q codeletion and IDH mutation have been shown to be closely associated with oligodendroglial phenotype and better prognosis. We sought to identify relevant biomarkers in non 1p/19q codeleted LGGs. METHODS: We characterized a retrospective series of 126 LGGs using genomic arrays, microsatellite analysis, IDH sequencing, MGMT promoter methylation assay, and p53 expression analysis. RESULTS: Our study confirms that 1p/19q codeletion, mutually exclusive with p53 overexpression, was associated with: (i) better prognosis, (ii) oligodendroglial phenotype, (iii) MGMT promoter methylation, and (iv) IDH mutation. Interestingly, 1p/19q codeleted tumors occur in older patients at diagnosis. Our study shows that non 1p/19q codeleted LGGs can be divided in 5 main genomic subgroups: (i) 11p loss, (ii) 19q loss (iii) 7 gain, (iv) 19 gain, and (v) unclassified. In non 1p/19q codeleted LGGs, we demonstrated that (i) 11p loss is associated with astrocytoma phenotype and has an independent negative prognostic value, and (ii) 19q loss diminished the favorable prognostic value of IDH mutation. Our findings were validated in an independent cohort of 98 LGGs. CONCLUSION: Novel genomic entities and biomarkers have been identified in non 1p/19q codeleted LGGs. Our findings may help to stratify non 1p/19q codeleted LGGs, facilitating future individualization of treatment. Further prospective studies are warranted to support our findings.
Published: 2014

42. Polymorphism in Sp1 recognition site of the EGF receptor gene promoter and risk of glioblastoma

Author: Joëlle Thillet, M. Sanson, N. Auger, Julie Lejeune, Florence Laigle-Donadey, Y. Marie, Gentian Kaloshi, J.-Y. Delattre, Alexandra Benouaich-Amiel, and Catherine Carpentier
Subjects: Adult, Male, Sp1 Transcription Factor, Central nervous system disease, Gene Frequency, Risk Factors, Polymorphism (computer science), Genotype, Odds Ratio, medicine, Humans, Prospective Studies, RNA, Messenger, Epidermal growth factor receptor, Allele, Risk factor, Promoter Regions, Genetic, Receptor, Alleles, Aged, Chi-Square Distribution, Polymorphism, Genetic, biology, Reverse Transcriptase Polymerase Chain Reaction, Promoter, Middle Aged, medicine.disease, Survival Analysis, ErbB Receptors, Cancer research, biology.protein, Female, Neurology (clinical), Glioblastoma, Follow-Up Studies
Abstract: We investigated two polymorphisms of the epidermal growth factor receptor promoter as potential risk factors and prognostic markers for glioblastoma. The -216T allele (which results in a 30% higher activity) was more frequent in the patients compared with the control population (224/376 = 59.6% vs 165/352 = 46.8%; p = 0.0006) corresponding to an odd ratio of 1.67 (1.24; 2.25). A modest difference in median survival was also associated with the TT genotype.
Published: 2006

43. Prevalence, clinico-pathological value, and co-occurrence of PDGFRA abnormalities in diffuse gliomas

Author: Jean Yves Delattre, Yannick Marie, Ahmed Idbaih, Karima Mokhtari, Marc Sanson, Khê Hoang-Xuan, Catherine Carpentier, Marianne Labussière, Blandine Boisselier, Agusti Alentorn, and Marine Giry
Subjects: Adult, Male, Cancer Research, Receptor, Platelet-Derived Growth Factor alpha, Clinical Investigations, PDGFRA, Kaplan-Meier Estimate, Biology, Disease-Free Survival, Fusion gene, Exon, Glioma, Gene duplication, medicine, Prevalence, Humans, Proportional Hazards Models, Brain Neoplasms, Reverse Transcriptase Polymerase Chain Reaction, Point mutation, Gene Amplification, Middle Aged, medicine.disease, Prognosis, digestive system diseases, Real-time polymerase chain reaction, Oncology, Mutation, Cancer research, Female, Neurology (clinical), Neoplasm Grading, PDGFRA Gene Amplification
Abstract: PDGFRA is a critical gene in glioma biology. Similar to EGFR, PDGFRA has been shown to be overexpressed, amplified, mutated, or truncated in gliomas, particularly glioblastomas. In addition, PDGFRA has been recently shown to be rearranged in glioblastoma. However, the frequency, cooccurrence, and clinical value of PDGFRA abnormalities in diffuse gliomas remain unclear. We investigated PDGFRA abnormalities and their clinical impact on 619 primary diffuse gliomas, including 167 grade II, 168 grade III, and 284 grade IV gliomas, with use of BAC-aCGH and validated our findings by quantitative polymerase chain reaction (PCR). We studied PDGFRA expression using reverse-transcription quantitative PCR in 84 gliomas and 12 non-tumor samples. In 138 samples, we also screened PDGFRA point mutations in exons 5, 7, 8, 9, 10, 11, and 23; presence of KDR-PDGFRA fusion gene; and PDGFRA truncation. PDGFRA was amplified and gained in 5.2% and 1.9% of samples, respectively. In addition PDGFRA was point-mutated, rearranged, and truncated in 2.9%, 0%, and 0.7% of cases, respectively. PDGFRA point mutations were observed exclusively in grade IV gliomas and in 12.5% of PDGFRA-amplified tumors. High-level PDGFRA amplification was associated with PDGFRA overexpression, high malignancy grade, and older patient age. Of interest, high-level PDGFRA amplification has an independent negative prognostic value for progression-free survival and overall survival among patients with grade III tumors. PDGFRA is altered through various genetic mechanisms in a subset of high-grade gliomas in patients who might be ideal candidates for PDGFRA inhibitor treatment, and PDGFRA gene amplification could be used as a prognostic biomarker in anaplastic gliomas.
Published: 2012

44. Validation of the new glioma WHO classification in the french POLA network: Analysis of 1041 cases

Author: Caroline Dehais, Jean-Yves Delattre, François Ducray, Ahmed Idbaih, Anne Jouvet, Anh Tuan Nguyen, Emeline Tabouret, Laura Lebouil, Dominique Figarella-Branger, Emmanuelle Uro-Coste, Catherine Carpentier, and Karima Moktari
Subjects: Cancer Research, Computational biology, 030204 cardiovascular system & hematology, Biology, medicine.disease, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Glioma, medicine, Who classification, Network analysis
Abstract: 2015Background: The upcoming WHO classification of gliomas will be refined taking into account the robust molecular alterations of gliomagenesis: the 1p19q codeletion and IDH1/2mutations. Methods: ...
Published: 2016

45. SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas

Author: Emmanuelle Uro-Coste, Luc Bauchet, Jean-Yves Delattre, Caroline Le Guerinel, Phong Dam-Hieu, Christine Desenclos, Alexandra Benouaich-Amiel, Thierry Faillot, Catherine Carpentier, Delphine Loussouarn, Antoine F. Carpentier, Karima Mokhtari, François Labrousse, Georges Noël, Olivier Chinot, Jérôme Honnorat, Simon de Bernard, François Ghiringhelli, Ahmed Idbaih, Pierre Verelle, Selma Elouadhani-Hamdi, Sandrine Eimer, Emmanuelle Lechapt-Zalcman, Dominique Figarella-Branger, Marie Janette Motsuo Fotso, Patrick Beauchesne, Frédéric Dhermain, Joel Godard, Anne Jouvet, Caroline Dehais, Carole Ramirez, Philippe Menei, Célia Courdy, Philippe Colin, Elodie Vauleon, Olivier Langlois, François Ducray, Denys Fontaine, Fabrice Parker, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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), UPMC - Département de neurologie 2 - Mazarin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Référence Maladie Rare 'Syndromes neurologiques Paranéoplasiques', Hospices Civils de Lyon (HCL)-Hopital Neurologique, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), AltraBio [Lyon], Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Clinique de Neurochirurgie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neuro-Oncologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Services de Neurologie [CHU Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Service de Neurochirurgie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire d'Histologie et de Pathologie moléculaire des tumeurs, Université Bordeaux Segalen - Bordeaux 2-EA 2406, Service de neurochirurgie [Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratoire d'Anatomie Pathologique [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), Université Paris Diderot - Paris 7 (UPD7), 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), Service de neurochirurgie, Hôpital Beaujon [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), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de neurochirurgie [AP-HP Hôpital Lariboisière], AP-HP Groupe Hospitalier Lariboisière, 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), Centre d'Études Préhistoire, Antiquité, Moyen-Age (CEPAM), Université Nice Sophia Antipolis (... - 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), 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 Neurochirurgie, Centre Hospitalier Universitaire de Nice (CHU Nice), CRLCC Eugène Marquis (CRLCC), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Service de Neurochirurgie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Hôpital Nord (Saint Etienne), Service de Neurochirurgie [CHU Amiens], CHU Amiens-Picardie, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Paul Strauss, CRLCC Paul Strauss, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-CHU Limoges, Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Université de Limoges (UNILIM), Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), Stéroides et système nerveux : physiopathologie moléculaire et clinique, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), This work is funded by the French Institut National du Cancer (INCa) and part of the national program Cartes d’Identite´ des Tumeurs H (CIT) (http://cit.liguecancer.net/) funded and developed by the Ligue nationale contre le cancer., Sindou, Philippe, 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)-Sorbonne Université (SU)-Sorbonne Université (SU), 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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département Neurologie [CHU Toulouse], Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut des Neurosciences de Montpellier (INM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Neurochirurgie [CHRU Besançon], 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), Service de neurochirurgie [CHU Angers], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]
Subjects: Male, MESH: Genes, p16, Pathology, Tumor Physiology, Loss of Heterozygosity, Loss of heterozygosity, 0302 clinical medicine, CDKN2A, Gene duplication, Molecular Cell Biology, Basic Cancer Research, MESH: Aged, Multidisciplinary, MESH: Middle Aged, Brain Neoplasms, MESH: Polymorphism, Single Nucleotide, Genomics, Middle Aged, 3. Good health, Neurology, Oncology, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, Medicine, Female, Research Article, Adult, medicine.medical_specialty, IDH1, Histology, MESH: Mutation, Science, Oligodendroglioma, Locus (genetics), [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, IDH2, Polymorphism, Single Nucleotide, 03 medical and health sciences, medicine, Genetics, Cancer Genetics, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Oligodendroglioma, Aged, MESH: Loss of Heterozygosity, MESH: Humans, Genes, p16, Chromosome, MESH: Adult, medicine.disease, MESH: Male, MESH: Gene Deletion, Mutation, MESH: Female, 030217 neurology & neurosurgery, Gene Deletion, Neuroscience
Abstract: International audience; Anaplastic oligodendrogliomas (AOD) are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19)(q10;p10), IDH1, IDH2, CIC and FUBP1 mutations).To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA)," has been supported by the Institut National du Cancer (InCA). Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples) were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH) inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD.
Published: 2012

46. P17.01 * CHROMOSOME ARM 9P LOSS OF HETEROZYGOSITY IS A MARKER OF SHORTER SURVIVAL IN 1P/19Q CO-DELETED ANAPLASTIC OLIGODENDROGLIOMA. A POLA NETWORK STUDY

Author: Agusti Alentorn, Dominique Figarella-Branger, Karima Mokhtari, Ahmed Idbaih, Catherine Carpentier, Caroline Dehais, Jean Yves Delattre, and François Ducray
Subjects: Oncology, Cancer Research, Univariate analysis, Pathology, medicine.medical_specialty, business.industry, Single-nucleotide polymorphism, medicine.disease, Poster Presentations, Loss of heterozygosity, Internal medicine, Glioma, Medicine, Oligodendroglial Tumor, Clinical significance, Neurology (clinical), Oligodendroglioma, business, Prospective cohort study
Abstract: Anaplastic or WHO grade III oligodendrogliomas (AO) are a heterogeneous subgroup of diffuse glial tumors in adults. Three major histomolecular subtypes with clinical relevance have been individualized: (i) 1p/19q co-deleted AO -80% of cases-, (ii) non 1p/19q co-deleted and IDH mutated AO -10% of cases- and (iii) non 1p/19q co-deleted and IDH wild-typeAO -10% of cases-. 1p/19q co-deleted AO, and to a lesser extent IDH mutated AO, have better prognosis and better response to treatment with a median survival of more than 10 years, as shown in two phase III international trials. We have recently shown that loss of heterozygosity (LOH) in chromosome arm 9p, with copy number loss -CL LOH- or without -Copy Neutral LOH- is a frequent event in AO. Interestingly, 9p CN LOH, inducing gene under-expression, has biological significance. In the present study, we address the prognostic value of 9p loss in 1p/19q co-deleted AO. In the present study, 228 AO exhibiting 1p/19q co-deletion were included. All tumors were centrally reviewed in the setting of the French national network for high-grade oligodendroglial tumors (POLA network) that recruits prospectively newly diagnosed anaplastic oligodendroglial tumors. Tumor DNA was analyzed using high-resolution single nucleotide polymorphism array analysis. In the entire series, 70/228 (1/3) harbored 9p loss including CN-LOH, homozygous loss or CL-LOH. 9p loss was associated with a worse prognosis in 1p19q co-deleted AO in univariate analysis (3-years OS of 98% vs. 74%, p < 0.001) whereas PFS at three years was not significantly different (3-years PFS of 88% vs. 66% p = 0.1). After adjustment for age, KPS, and treatment, multivariate analysis demonstrated 9p loss to be an independent prognostic factor for OS, p-value = 0.03, HR = 4.9 [1.2-16], but not for PFS. 1p19q co-deleted AO harboring 9p loss have shorter overall survival compared to their non 9p-lost counterparts in this prospective cohort. Further studies are needed to validate our findings.
Published: 2014

47. Genetic risk profiles identify different molecular etiologies for glioma

Author: Yannick Marie, Karima Mokhtari, Richard S. Houlston, Khê Hoang-Xuan, Fay J. Hosking, Catherine Carpentier, Matthias Simon, Konstantinos Gousias, Mark Lathrop, Jean-Yves Delattre, Marc Sanson, Ahmed Idbaih, Johannes Schramm, Lindsay B. Robertson, and Blandine Boisselier
Subjects: Adult, Male, Risk, Oncology, Cancer Research, medicine.medical_specialty, Genotype, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, Cohort Studies, Young Adult, Gene Frequency, CDKN2A, Glioma, Internal medicine, medicine, Humans, SNP, Genetic Predisposition to Disease, Risk factor, Allele frequency, Survival analysis, Genetic association, Brain Neoplasms, Gene Expression Profiling, 610 Medical sciences, Medicine, Middle Aged, medicine.disease, Survival Analysis, ddc: 610, Immunology, Female
Abstract: Objective: Genome-wide association studies have recently identified single nucleotide polymorphisms in five loci at 5p15.33 (rs2736100, TERT), 8q24.21 (rs4295627, CCDC26), 9p21.3 (rs4977756, CDKN2A/CDKN2B), 20q13.33 (rs6010620, RTEL1) and 11q23.3 (rs498872, PHLDB1) to be associated with glioma [for full text, please go to the a.m. URL], 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010
Published: 2010

48. Diagnostic and prognostic value of alpha internexin expression in a series of 409 gliomas

Author: Charles Duyckaerts, Sophie Paris, Catherine Carpentier, Caroline Dehais, Khê Hoang-Xuan, Jean-Yves Delattre, Marie-José Dieme, François Ducray, Yannick Marie, Clovis Adam, Karima Mokhtari, Ahmed Idbaih, Marc Sanson, and Emmanuelle Crinière
Subjects: Adult, Cancer Research, medicine.medical_specialty, Pathology, IDH1, Gastroenterology, IDH2, Disease-Free Survival, Intermediate Filament Proteins, Internal medicine, Biomarkers, Tumor, Medicine, Humans, Progression-free survival, neoplasms, business.industry, Brain Neoplasms, Cancer, Histology, Glioma, medicine.disease, Prognosis, Immunohistochemistry, Isocitrate Dehydrogenase, nervous system diseases, Oncology, Mutation, Oligodendroglioma, Tumor Suppressor Protein p53, business, Anaplastic astrocytoma
Abstract: The neuronal intermediate filament alpha internexin (INA) is expressed in most gliomas with 1p19q codeletion and could represent a valuable prognostic marker in clinical routine. INA expression was analysed on 409 gliomas and correlated with histology, progression free survival (PFS), overall survival (OS), genomic profile assessed by CGH-array, IDH1/IDH2 mutation and p53 expression. INA was expressed in 59% of grade II oligodendrogliomas (n=73), 45% of grade III oligodendrogliomas (n=133), 15% of grade II oligoastrocytomas (n=61), 12% of grade III oligoastrocytomas (n=41), 23% of glioblastomas with oligodendroglial component (n=31), 0% of grade I astrocytomas (n=3), 0% of grade II astrocytomas (n=14), 6% of grade III astrocytomas (n=17) and 0% of glioblastomas (n=36). INA expression was detected in 85% of gliomas with complete 1p19q codeletion ('true 1p19q signature') (n=85) versus 15% of gliomas without 1p19q codeletion (n=245), including 14% of gliomas with variable/partial 1p19q deletion ('false 1p19q signature') (n=72) (p
Published: 2010

49. Chromosome 9p and 10q losses predict unfavorable outcome in low-grade gliomas

Author: Marc Sanson, Catherine Carpentier, Khê Hoang-Xuan, Julien Laffaire, Gentian Kaloshi, Florence Laigle-Donadey, Audrey Rousseau, Caroline Dehais, Karima Mokhtari, Yannick Marie, Caroline Houillier, Emmanuelle Crinière, and Jean-Yves Delattre
Subjects: Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Adolescent, Loss of Heterozygosity, Kaplan-Meier Estimate, Biology, Bioinformatics, Disease-Free Survival, Loss of heterozygosity, Young Adult, Internal medicine, Glioma, medicine, Humans, Progression-free survival, Young adult, neoplasms, Aged, Univariate analysis, Karnofsky Performance Status, Tumor size, Brain Neoplasms, Chromosomes, Human, Pair 10, Chromosome, Middle Aged, medicine.disease, Prognosis, Female, Rapid Reports, Neurology (clinical), Chromosomes, Human, Pair 9, Microsatellite Repeats
Abstract: The prognosis of low-grade gliomas (LGGs) varies widely, with overall survival (OS) ranging from a few years to decades. Defining reliable prognostic factors in LGGs has been difficult, but the importance of clinical factors, including gender, age, Karnofsky performance status (KPS), symptoms at diagnosis, tumor size, and extent of tumor resection, has been recently recognized.1–4 To date, the only identified molecular alteration of prognostic importance in LGGs is the 1p–19q co-deletion.5,6 Loss of heterozygosity (LOH) on chromosomes 9p and 10q is rare in LGGs. These alterations are classically associated with high-grade tumors (anaplastic gliomas and glioblastomas)7 and have been found to be of prognostic significance in anaplastic gliomas8 but not in glioblastomas.9 In this study, we analyzed the prognostic impact of LOH on 9p and 10q in a series of LGGs.
Published: 2010

50. Genomic changes in progression of low-grade gliomas

Author: Khê Hoang-Xuan, Jean-Yves Delattre, Sophie Taillibert, Joëlle Thillet, Yannick Marie, Rosana Carvalho Silva, François Ducray, Marc Sanson, Audrey Rousseau, Karima Mokhtari, Catherine Carpentier, Emmanuelle Crinière, Blandine Boisselier, Ahmed Idbaih, Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Laboratoire de Neuropathologie Raymond Escourolle, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Idbaih, Ahmed, 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)-Sorbonne Université (SU), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Adult, Male, Cancer Research, Candidate gene, Locus (genetics), [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, Chromosomes, 03 medical and health sciences, 0302 clinical medicine, CDKN2A, Glioma, medicine, Humans, 030304 developmental biology, Genetics, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Genome, Nucleic Acid Hybridization, Chromosome, Middle Aged, medicine.disease, 3. Good health, Neurology, Oncology, MSH3, Tumor progression, 030220 oncology & carcinogenesis, Disease Progression, Cancer research, Female, Neurology (clinical), Chromosome Deletion, Microsatellite Repeats, Comparative genomic hybridization
Abstract: International audience; Using a one-megabase BAC-based array comparative genomic hybridization technique (aCGH), we have investigated a series of 16 low-grade gliomas (LGGs) and their subsequent progression to higher-grade malignancies. The most frequent chromosome imbalances in primary tumors were gains of chromosomes 7q, 8q, and 22q, and losses of chromosomes 1p, 13q, and 19q. In tumor progression, gains of chromosomes 11q, 7q, 20q, and 21q, and losses of chromosomes 9p, including CDKN2A locus, 19q, 14q, 1p, and 6q were the most frequent genomic disequilibria. Progressive tumors were more imbalanced than primary tumors in terms of altered chromosomal arms (3.8 vs. 6.6 in mean abnormal chromosomal arm) and altered BACs (17 vs. 21%). Interestingly, putative novel candidate genes associated with glioma progression were identified, in particular DOCK8, PTPRD, CER1, TPHO, DHFR, MSH3, ETS1, ACACA, and CSE1L.
Published: 2008

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