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14 results on '"Puget, Stéphanie"'

1. Imaging features to distinguish posterior fossa ependymoma subgroups

Author

Leclerc, Thomas, Levy, Raphael, Tauziède-Espariat, Arnault, Roux, Charles-Joris, Beccaria, Kevin, Blauwblomme, Thomas, Puget, Stéphanie, Grill, Jacques, Dufour, Christelle, Guerrini-Rousseau, Léa, Abbou, Samuel, Bolle, Stéphanie, Roux, Alexandre, Pallud, Johan, Provost, Corentin, Oppenheim, Catherine, Varlet, Pascale, Boddaert, Nathalie, and Dangouloff-Ros, Volodia

Published
2024
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2. Clear cell meningiomas are defined by a highly distinct DNA methylation profile and mutations in SMARCE1

Author

Sievers, Philipp, Sill, Martin, Blume, Christina, Tauziede-Espariat, Arnault, Schrimpf, Daniel, Stichel, Damian, Reuss, David E, Dogan, Helin, Hartmann, Christian, Mawrin, Christian, Hasselblatt, Martin, Stummer, Walter, Schick, Uta, Hench, Jürgen, Frank, Stephan, Ketter, Ralf, Schweizer, Leonille, Schittenhelm, Jens, Puget, Stéphanie, Brandner, Sebastian, Jaunmuktane, Zane, Küsters, Benno, Abdullaev, Zied, Pekmezci, Melike, Snuderl, Matija, Ratliff, Miriam, Herold-Mende, Christel, Unterberg, Andreas, Aldape, Kenneth, Ellison, David W, Wesseling, Pieter, Reifenberger, Guido, Wick, Wolfgang, Perry, Arie, Varlet, Pascale, Pfister, Stefan M, Jones, David TW, von Deimling, Andreas, and Sahm, Felix

Subjects
Human Genome, Brain Disorders, Pediatric, Cancer, Genetics, Rare Diseases, Brain Cancer, Aetiology, 2.1 Biological and endogenous factors, Brain Neoplasms, Child, Chromosomal Proteins, Non-Histone, Cohort Studies, DNA Methylation, DNA Mutational Analysis, DNA, Neoplasm, DNA-Binding Proteins, Disease Progression, Epigenesis, Genetic, Female, Genome-Wide Association Study, Humans, Immunohistochemistry, Male, Meningioma, Mutation, Neoplasm Recurrence, Local, Treatment Outcome, Young Adult, Brain tumor, Clear cell, SMARCE1, DNA methylation profile, German Consortium “Aggressive Meningiomas”, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Clear cell meningioma represents an uncommon variant of meningioma that typically affects children and young adults. Although an enrichment of loss-of-function mutations in the SMARCE1 gene has been reported for this subtype, comprehensive molecular investigations are lacking. Here we describe a molecularly distinct subset of tumors (n = 31), initially identified through genome-wide DNA methylation screening among a cohort of 3093 meningiomas, of which most were diagnosed histologically as clear cell meningioma. This cohort was further supplemented by an additional 11 histologically diagnosed clear cell meningiomas for analysis (n = 42). Targeted DNA sequencing revealed SMARCE1 mutations in 33/34 analyzed samples, accompanied by a nuclear loss of expression determined via immunohistochemistry and a decreased SMARCE1 transcript expression in the tumor cells. Analysis of time to progression or recurrence of patients within the clear cell meningioma group (n = 14) in comparison to those with meningioma WHO grade 2 (n = 220) revealed a similar outcome and support the assignment of WHO grade 2 to these tumors. Our findings indicate the existence of a highly distinct epigenetic signature of clear cell meningiomas, separate from all other variants of meningiomas, with recurrent mutations in the SMARCE1 gene. This suggests that these tumors may arise from a different precursor cell population than the broad spectrum of the other meningioma subtypes.

Published
2021

3. Germline Elongator mutations in Sonic Hedgehog medulloblastoma.

Author

Robinson, Giles, Gudenas, Brian, Smith, Kyle, Forget, Antoine, Kojic, Marija, Garcia-Lopez, Jesus, Hadley, Jennifer, Hamilton, Kayla, Indersie, Emilie, Buchhalter, Ivo, Kerssemakers, Jules, Jäger, Natalie, Sharma, Tanvi, Rausch, Tobias, Kool, Marcel, Sturm, Dominik, Jones, David, Vasilyeva, Aksana, Tatevossian, Ruth, Neale, Geoffrey, Lombard, Bérangère, Loew, Damarys, Nakitandwe, Joy, Rusch, Michael, Bowers, Daniel, Bendel, Anne, Partap, Sonia, Chintagumpala, Murali, Crawford, John, Gottardo, Nicholas, Smith, Amy, Dufour, Christelle, Rutkowski, Stefan, Eggen, Tone, Wesenberg, Finn, Kjaerheim, Kristina, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina, Röösli, Martin, Kuehni, Claudia, Grotzer, Michael, Remke, Marc, Puget, Stéphanie, Pajtler, Kristian, Milde, Till, Witt, Olaf, Ryzhova, Marina, Korshunov, Andrey, Orr, Brent, Ellison, David, Brugieres, Laurence, Lichter, Peter, Nichols, Kim, Gajjar, Amar, Wainwright, Brandon, Ayrault, Olivier, Korbel, Jan, Northcott, Paul, Pfister, Stefan, and Waszak, Sebastian

Subjects
Cerebellar Neoplasms, Child, Female, Germ-Line Mutation, Humans, Male, Medulloblastoma, Pedigree, RNA, Transfer, Transcriptional Elongation Factors
Abstract

Cancer genomics has revealed many genes and core molecular processes that contribute to human malignancies, but the genetic and molecular bases of many rare cancers remains unclear. Genetic predisposition accounts for 5 to 10% of cancer diagnoses in children1,2, and genetic events that cooperate with known somatic driver events are poorly understood. Pathogenic germline variants in established cancer predisposition genes have been recently identified in 5% of patients with the malignant brain tumour medulloblastoma3. Here, by analysing all protein-coding genes, we identify and replicate rare germline loss-of-function variants across ELP1 in 14% of paediatric patients with the medulloblastoma subgroup Sonic Hedgehog (MBSHH). ELP1 was the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% among paediatric patients with MBSHH. Parent-offspring and pedigree analyses identified two families with a history of paediatric medulloblastoma. ELP1-associated medulloblastomas were restricted to the molecular SHHα subtype4 and characterized by universal biallelic inactivation of ELP1 owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1, which suggests that germline ELP1 loss-of-function variants predispose individuals to tumour development in combination with constitutive activation of SHH signalling. ELP1 is the largest subunit of the evolutionarily conserved Elongator complex, which catalyses translational elongation through tRNA modifications at the wobble (U34) position5,6. Tumours from patients with ELP1-associated MBSHH were characterized by a destabilized Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to Elongator deficiency in model systems7-9. Thus, genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers. These results support investigation of the role of protein homeostasis in other cancer types and potential for therapeutic interference.

Published
2020

4. Radiogenomics of diffuse intrinsic pontine gliomas (DIPGs): correlation of histological and biological characteristics with multimodal MRI features

Author

Calmon, Raphaël, Dangouloff-Ros, Volodia, Varlet, Pascale, Deroulers, Christophe, Philippe, Cathy, Debily, Marie-Anne, Castel, David, Beccaria, Kevin, Blauwblomme, Thomas, Grevent, David, Levy, Raphael, Roux, Charles-Joris, Purcell, Yvonne, Saitovitch, Ana, Zilbovicius, Monica, Dufour, Christelle, Puget, Stéphanie, Grill, Jacques, and Boddaert, Nathalie

Published
2021
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6. Biological material collection to advance translational research and treatment of children with CNS tumours: position paper from the SIOPE Brain Tumour Group

Author

Rutkowski, Stefan, Modena, Piergiorgio, Williamson, Daniel, Kerl, Kornelius, Nysom, Karsten, Pizer, Barry, Bartels, Ute, Puget, Stéphanie, Doz, François, Michalski, Antony, von Hoff, Katja, Chevignard, Mathilde, Avula, Shivaram, Murray, Matthew, Schönberger, Stefan, Czech, Thomas, Schouten-van Meeteren, Antoinette, Kordes, Uwe, Kramm, Chris, van Vuurden, Dannis, Hulleman, Esther, Janssens, Geert, Solanki, Guirish, van Veelen, Marie-Luise, Thomale, Ulrich, Schuhmann, Martin, Jones, Chris, Giangaspero, Felice, Figarella-Branger, Dominique, Pietsch, Torsten, Clifford, Steve, Pfister, Stefan, Van Gool, Stefaan, Kramm, Christof, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Department of Pediatric Oncology, Alder Hey Children's Hospital, Alder Hey Children's Hospital, Department of Paediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France., Institut Curie [Paris], Laboratoire d'Imagerie Biomédicale (LIB), 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), Medizinische Universität Wien = Medical University of Vienna, Cavendish Laboratory, University of Cambridge [UK] (CAM), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of Bonn, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University Hospital Gasthuisberg, Expt Immunol Lab, Université Catholique de Louvain = Catholic University of Louvain (UCL), 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), Neurosurgery, Murray, Matthew [0000-0002-4480-1147], and Apollo - University of Cambridge Repository

Subjects
standards [Biological Specimen Banks], 0301 basic medicine, Male, standards [Medical Oncology], medicine.medical_specialty, methods [Translational Research, Biomedical], organization & administration [Translational Research, Biomedical], [SDV]Life Sciences [q-bio], MEDLINE, ethics [Biological Specimen Banks], Translational research, standards [Translational Medical Research], Disease, standards [Translational Research, Biomedical], Medical Oncology, organization & administration [Biological Specimen Banks], Central Nervous System Neoplasms, Translational Research, Biomedical, 03 medical and health sciences, 0302 clinical medicine, medicine, Biomarkers, Tumor, Humans, ddc:610, methods [Translational Medical Research], organization & administration [Medical Oncology], CNS tumours, childhood cancer, SIOPE Brain Tumour Group, biological material, Medical diagnosis, Intensive care medicine, Child, Biological Specimen Banks, business.industry, Precision medicine, Biobank, 3. Good health, Data sharing, 030104 developmental biology, trends [Medical Oncology], Oncology, organization & administration [Translational Medical Research], 030220 oncology & carcinogenesis, Position paper, Female, business
Abstract

International audience; Paediatric CNS tumours are the most common cause of childhood cancer-related morbidity and mortality, and improvements in their diagnosis and treatment are needed. New genetic and epigenetic information about paediatric CNS tumours is transforming the field dramatically. For most paediatric CNS tumour entities, subgroups with distinct biological characteristics have been identified, and these characteristics are increasingly used to facilitate accurate diagnoses and therapeutic recommendations. Future treatments will be further tailored to specific molecular subtypes of disease, specific tumour predisposition syndromes, and other biological criteria. Successful biomaterial collection is a key requirement for the application of contemporary methodologies for the validation of candidate prognostic factors, the discovery of new biomarkers, the establishment of appropriate preclinical research models for targeted agents, a quicker clinical implementation of precision medicine, and for other therapeutic uses (eg, for immunotherapies). However, deficits in organisational structures and interdisciplinary cooperation are impeding the collection of high-quality biomaterial from CNS tumours in most centres. Practical, legal, and ethical guidelines for consent, storage, material transfer, biobanking, data sharing, and funding should be established by research consortia and local institutions to allow optimal collection of primary and subsequent tumour tissue, body fluids, and normal tissue. Procedures for the collection and storage of biomaterials and related data should be implemented according to the individual and organisational structures of the local institutions.

Published
2018
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7. Childhood supratentorial ependymomas with YAP1- MAMLD1 fusion: an entity with characteristic clinical, radiological, cytogenetic and histopathological features

Author

Andreiuolo, Felipe, Varlet, Pascale, Tauziède‐Espariat, Arnault, Jünger, Stephanie T., Dörner, Evelyn, Dreschmann, Verena, Kuchelmeister, Klaus, Waha, Andreas, Haberler, Christine, Slavc, Irene, Corbacioglu, Selim, Riemenschneider, Markus J., Leipold, Alfred, Rüdiger, Thomas, Körholz, Dieter, Acker, Till, Russo, Alexandra, Faber, Jörg, Sommer, Clemens, Armbrust, Sven, Rose, Martina, Erdlenbruch, Bernhard, Hans, Volkmar H., Bernbeck, Benedikt, Schneider, Dominik, Lorenzen, Johann, Ebinger, Martin, Handgretinger, Rupert, Neumann, Manuela, van Buiren, Miriam, Prinz, Marco, Roganovic, Jelena, Jakovcevic, Antonia, Park, Sung‐Hye, Grill, Jacques, Puget, Stéphanie, Messing‐Jünger, Martina, Reinhard, Harald, Bergmann, Markus, Hattingen, Elke, and Pietsch, Torsten

Subjects
Male, ependymoma, DNA Copy Number Variations, supratentorial, Infant, Nuclear Proteins, Supratentorial Neoplasms, YAP-Signaling Proteins, Phosphoproteins, YAP1-MAMLD1 fusion, childhood, DNA-Binding Proteins, YAP1‐MAMLD1 fusion, Child, Preschool, Humans, Female, Child, Research Articles, Research Article, Adaptor Proteins, Signal Transducing, Retrospective Studies, Transcription Factors
Abstract

Ependymoma with YAP1‐MAMLD1 fusion is a rare, recently described supratentorial neoplasm of childhood, with few cases published so far. We report on 15 pediatric patients with ependymomas carrying YAP1‐MAMLD1 fusions, with their characteristic histopathology, immunophenotype and molecular/cytogenetic, radiological and clinical features. The YAP1‐MAMLD1 fusion was documented by RT‐PCR/Sanger sequencing, and tumor genomes were studied by molecular inversion probe (MIP) analysis. Significant copy number alterations were identified by GISTIC (Genomic Identification of Significant Targets in Cancer) analysis. All cases showed similar histopathological features including areas of high cellularity, presence of perivascular pseudo‐rosettes, small to medium‐sized nuclei with characteristic granular chromatin and strikingly abundant cells with dot‐like cytoplasmic expression of epithelial membrane antigen. Eleven cases presented features of anaplasia, corresponding to WHO grade III. MRI showed large supratentorial multinodular tumors with cystic components, heterogeneous contrast enhancement, located in the ventricular or periventricular region. One of two variants of YAP1‐MAMLD1 fusions was detected in all cases. The MIP genome profiles showed balanced profiles, with focal alterations of the YAP1 locus at 11q22.1–11q21.2 (7/14), MAMLD1 locus (Xp28) (10/14) and losses of chromosome arm 22q (5/14). Most patients were female (13/15) and younger than 3 years at diagnosis (12/15; median age, 8.2 months). Apart from one patient who died during surgery, all patients are alive without evidence of disease progression after receiving different treatment protocols, three without postoperative further treatment (median follow‐up, 4.84 years). In this to date, largest series of ependymomas with YAP1‐MAMLD1 fusions we show that they harbor characteristic histopathological, cytogenetic and imaging features, occur mostly in young girls under 3 years and are associated with good outcome. Therefore, this genetically defined neoplasm should be considered a distinct disease entity. The diagnosis should be confirmed by demonstration of the specific fusion. Further studies on large collaborative series are warranted to confirm our findings.

Published
2018
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8. Maternal residential pesticide use during pregnancy and risk of malignant childhood brain tumors: A pooled analysis of the ESCALE and ESTELLE studies (SFCE)

Author

Vidart d'Egurbide Bagazgoïtia, Nicolas, Bailey, Helen, Orsi, Laurent, Lacour, Brigitte, Guerrini-Rousseau, Léa, Bertozzi, Anne-Isabelle, Leblond, Pierre, Faure-Conter, Cécile, Pellier, Isabelle, Freycon, Claire, Doz, François, Puget, Stéphanie, Ducassou, Stephane, Clavel, Jacqueline, Equipe 7 : EPICEA - Epidémiologie des cancers de l'enfant et de l'adolescent (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Registre National des Tumeurs Solides de l'Enfant (RNTSE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Cancéropôle du Grand Est, Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Oscar Lambret Comprehensive Cancer Center, Centre Léon Bérard [Lyon], Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut Curie [Paris], PRES Sorbonne Paris Cité, CHU de Bordeaux Pellegrin [Bordeaux], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), and Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, Risk, Adolescent, Brain Neoplasms, [SDV]Life Sciences [q-bio], Environmental Exposure, Young Adult, Pregnancy, Maternal Exposure, Prenatal Exposure Delayed Effects, Case-Control Studies, Humans, Female, France, Pesticides, Child, Preschool
Abstract

International audience; Some previous epidemiological studies have suggested that pesticide exposure during pregnancy may have a possible role in the development of childhood brain tumors (CBT). We pooled data from two French national population-based, case-control studies to investigate the association between maternal residential use of pesticides during pregnancy and the risk of CBT. The mothers of 437 CBT cases and 3,102 controls aged under 15 years who resided in France at diagnosis/interview, frequency-matched by age and gender, answered a structured telephone interview conducted by trained interviewers. Unconditional logistic regression was used to estimate pooled odds ratio (OR) and 95% confidence intervals (95% CI). CBT was significantly associated with the maternal home use of pesticides during pregnancy (OR 1.4, 95% CI 1.2-1.8) and, more specifically, with insecticide (OR 1.4, 1.2-1.8). We could not draw any conclusions about herbicides and/or fungicides because few women used them during pregnancy and most of these mothers also used insecticides. Although potential recall bias cannot be excluded, our findings of this pooled analysis support the hypothesis that residential maternal use of pesticides during pregnancy and particularly insecticides may increase the risk of CBT. Future investigations to verify these findings and to explore for CBT subtypes and dose-response are necessary to have a better understanding of the possible role of pesticides in etiology of CBT.

Published
2018
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9. Co-occurrence of histone H3 K27M and BRAF V600E mutations in paediatric midline grade I ganglioglioma

Author

Pagès, Mélanie, Beccaria, Kevin, Boddaert, Nathalie, El Saffroy, Raphael, Besnard, Aurore, Castel, David, Fina, Frederic, Barets, Doriane, Barret, Emilie, Lacroix, Ludovic, Bielle, Franck, Andreiuolo, Felipe, Tauziède-Espariat, Arnault, Figarella-Branger, Dominique, Puget, Stéphanie, Grill, Jacques, Chretien, Fabrice, Varlet, Pascale, Neuroimagerie en psychiatrie (U1000), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Département de biochimie, Ecole Polytechnique Féminine ((EPF)), Ecole d'Ingénieurs, Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], 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), Département de biologie et pathologie médicales [Gustave Roussy], 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), Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Centre National de la Recherche Scientifique (CNRS)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), 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), Institut Pasteur [Paris], Neuroimagerie en psychiatrie ( U1000 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Ecole Polytechnique Féminine ( (EPF) ), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] ( UMR 8203 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Gustave Roussy ( IGR ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital Nord [CHU - APHM], 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 ), Service de neuropathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], 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 ), figarella-branger, dominique, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, Proto-Oncogene Proteins B-raf, Adolescent, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Histones, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.CAN] Life Sciences [q-bio]/Cancer, H3 K27M, Humans, Spinal Cord Neoplasms, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Child, neoplasms, Research Articles, ganglioglioma, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Brain Neoplasms, BRAF V600E, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, midline, Immunohistochemistry, Treatment Outcome, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Child, Preschool, Mutation, Female, Neoplasm Grading, Follow-Up Studies
Abstract

International audience; Ganglioglioma (GG) is a grade I tumor characterized by alterations in the MAPK pathway, including BRAF V600E mutation. Recently, diffuse midline glioma with an H3 K27M mutation was added to the WHO 2016 classification as a new grade IV entity. As co-occurrence of H3 K27M and BRAF V600E mutations has been reported in midline tumors and anaplastic GG, we searched for BRAF V600E and H3 K27M mutations in a series of 54 paediatric midline grade I GG (midline GG) to determine the frequency of double mutations and its relevance for prognosis. Twenty-seven patients (50%) possessed the BRAF V600E mutation. The frequency of the co-occurrence of H3F3A/BRAF mutations at diagnosis was 9.3%. No H3 K27M mutation was detected in the absence of the BRAF V600E mutation. Double-immunostaining revealed that BRAF V600E and H3 K27M mutant proteins were present in both the glial and neuronal components. Immunopositivity for the BRAF V600E mutant protein correlated with BRAF mutation status as detected by massARRAY or digital droplet PCR. The median follow-up of patients with double mutation was 4 years. One patient died of progressive disease 8 years after diagnosis, whereas the four other patients were all alive with stable disease at the last clinical follow-up (at 9 months, 1 year and 7 years) without adjuvant therapy. We demonstrate in this first series of midline GGs that the H3 K27M mutation can occur in association with the BRAF V600E mutation in grade I glioneuronal tumors. Despite the presence of H3 K27M mutations, these cases should not be graded and treated as grade IV tumors because they have a better spontaneous outcome than classic diffuse midline H3 K27M-mutant glioma. These data suggest that H3 K27M cannot be considered a specific hallmark of grade IV diffuse gliomas and highlight the importance of integrated histomolecular diagnosis in paediatric brain tumors.

Published
2018
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10. Loss of SMARCE1 expression is a specific diagnostic marker of clear cell meningioma: a comprehensive immunophenotypical and molecular analysis

Author

Tauziede‐Espariat, Arnault, Parfait, Béatrice, Besnard, Aurore, Lacombe, Joëlle, Pallud, Johan, Tazi, Sanaa, Puget, Stéphanie, Lot, Guillaume, Terris, Benoît, Cohen, Joëlle, Vidaud, Michel, Figarella‐Branger, Dominique, Monnien, Franck, Polivka, Marc, Adle‐Biassette, Homa, and Varlet, Pascale

Subjects
Adult, Male, Adolescent, Genotype, Chromosomal Proteins, Non-Histone, Middle Aged, Immunohistochemistry, Antibodies, DNA-Binding Proteins, Young Adult, Biomarkers, Tumor, Meningeal Neoplasms, Humans, Female, Child, Meningioma, Research Articles, Aged, Retrospective Studies
Abstract

Clear cell meningioma (CCM) is a rare grade II histopathological subtype that usually occurs in young patients and displays high recurrence rate. Germline SMARCE1 mutations have been described in hereditary forms of this disease and more recently in small syndromic and sporadic CCM series. The diagnostic value of SMARCE1 in distinguishing between CCM and other meningioma variants has not been yet established. The aim of our study was to investigate the status of SMARCE1 in a series of CCMs and its morphological mimickers. We compared the performance of an anti-SMARCE1 antibody and the molecular analysis of the SMARCE1 gene in a retrospective multicenter series of CCMs. All CCMs lossed SMARCE1 immunoexpression. Bi-allelic inactivating events were found by NGS-based sequencing in all of these cases, except for one, which was incompletely explored, but had a wild-type sequence. We then validated the anti-SMARCE1 antibody specificity by analyzing additional 305 pediatric and adult meningiomas of various subtypes and 15 non-meningioma clear cell tumors by SMARCE1 immunohistochemistry. A nuclear immunostaining was preserved in all other meningioma variants, as well as non-meningioma clear cell tumors. In conclusion, our series showed, for the first time, that SMARCE1 immunostaining is a highly sensitive biomarker for CCM, useful as a routine diagnostic biomarker.

Published
2017

11. A driver role for GABA metabolism in controlling stem and proliferative cell state through GHB production in glioma

Author

El-Habr, Elias A., Dubois, Luiz G., Burel-Vandenbos, Fanny, Bogeas, Alexandra, Lipecka, Joanna, Turchi, Laurent, Lejeune, François-Xavier, Coehlo, Paulo Lucas Cerqueira, Yamaki, Tomohiro, Wittmann, Bryan M., Fareh, Mohamed, Mahfoudhi, Emna, Janin, Maxime, Narayanan, Ashwin, Morvan-Dubois, Ghislaine, Schmitt, Charlotte, Verreault, Maité, Oliver, Lisa, Sharif, Ariane, Pallud, Johan, Devaux, Bertrand, Puget, Stéphanie, Korkolopoulou, Penelope, Varlet, Pascale, Ottolenghi, Chris, Plo, Isabelle, Moura-Neto, Vivaldo, Virolle, Thierry, Chneiweiss, Hervé, Junier, Marie-Pierre, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Instituto Estadual do cerebro Paulo Niemeyer, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Service de pathologie, Centre Hospitalier Universitaire de Nice (CHU Nice), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), 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)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Metabolon, Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biochimie métabolique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], 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], 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 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), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Université Paris Descartes - Paris 5 (UPD5), Department of Paediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France., Department of Haematopathology, National and Kapodistrian University of Athens, Laikon General Hospital, Service de neuropathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Sainte-Anne, Hématopoïèse normale et pathologique (U1170 Inserm), This work was supported by La Ligue nationale contre le cancer (Equipe Labellisée LIGUE 2013, Equipe Labelisée LIGUE 2016 HC/MPJ), Institut National du Cancer (INCa 2012-1-PLBIO-07-INSERM-1, HC/MPJ), Cancéropole Région Ile-de-France (EAE and AB fellowships), CAPES/COFECUB (Coordination pour le perfectionnement du personnel de l’enseignement supérieur/Comité français d’evaluation de la coopération universitaire et scientifique avec le Brésil, VMN and LGD fellowship), Fundação Ary Frauzino para o Câncer (LGD fellowship), and Neurosurgeon college of Chiba prefecture, Japan (TY fellowship)., Neuroscience Paris Seine ( NPS ), 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 ), Institut de Biologie Valrose ( IBV ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), CHU Nice, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing ( B2A ), 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 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Gustave Roussy ( IGR ) -Université Paris-Sud - Paris 11 ( UP11 ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), 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 ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-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 ), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Sainte-Anne, Hématopoïèse normale et pathologique ( U1170 Inserm ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [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 [APHP], Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Sainte-Anne, 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)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Centre de Psychiatrie et Neurosciences (U894), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université 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 Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, National and Kapodistrian University of Athens (NKUA), and Bernardo, Elizabeth

Subjects
Male, Carcinogenesis, Clinical Neurology, Hydroxybutyrates, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Brain cancer, Pathology and Forensic Medicine, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Cellular and Molecular Neuroscience, GABA, [SDV.CAN] Life Sciences [q-bio]/Cancer, Animals, Humans, ALDH5A1, Child, gamma-Aminobutyric Acid, Aged, Cell Proliferation, Original Paper, Valproate, Cell Death, Brain Neoplasms, Cancer stem cell, Brain, Glioma, Middle Aged, 5-hmC, Child, Preschool, Neoplastic Stem Cells, DIPG, Female, Succinate-Semialdehyde Dehydrogenase, Neoplasm Transplantation
Abstract

Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product GHB (4-hydroxybutyrate). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation. Enhancing GHB levels via SSADH downregulation or GHB supplementation triggered cell conversion into a less aggressive phenotypic state. GHB affected adult glioblastoma cells with varying molecular profiles, along with cells from pediatric pontine gliomas. In all cell types, GHB acted by inhibiting α-ketoglutarate-dependent Ten–eleven Translocations (TET) activity, resulting in decreased levels of the 5-hydroxymethylcytosine epigenetic mark. In patients, low SSADH expression was correlated with high GHB/α-ketoglutarate ratios, and distinguished weakly proliferative/differentiated glioblastoma territories from proliferative/non-differentiated territories. Our findings support an active participation of metabolic variations in the genesis of tumor heterogeneity. Electronic supplementary material The online version of this article (doi:10.1007/s00401-016-1659-5) contains supplementary material, which is available to authorized users.

Published
2016
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12. Clinical relevance of tumor cells with stem-like properties in pediatric brain tumors

Author

Thirant, Cécile, Bessette, Barbara, Varlet, Pascale, Puget, Stéphanie, Cadusseau, Josette, Dos Reis Tavares, Silvina, Studler, Jeanne-Marie, Silvestre, David Carlos, Susini, Aurélie, Villa, Chiara, Miquel, Catherine, Bogeas, Alexandra, Surena, Anne-Laure, Dias-Morais, Amélia, Léonard, Nadine, Pflumio, Françoise, Bièche, Ivan, Boussin, François D, Sainte-Rose, Christian, Grill, Jacques, Daumas-Duport, Catherine, Chneiweiss, Hervé, Junier, Marie-Pierre, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of neuropathology, Hôpial Sainte-Anne, Service de neurochirurgie pédiatrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), INSERM U955, équipe 10, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Collège de France (CdF (institution)), Stabilité génétique, Cellules Souches et Radiations (SCSR (U_967)), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Genetique Moleculaire des Cancers d'Origine Epitheliale, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris]

Subjects
MESH: Adolescent, MESH: Neural Stem Cells, child, MESH: Humans, MESH: Immunophenotyping, MESH: Child, Preschool, MESH: Flow Cytometry, medulloblastoma, MESH: Infant, MESH: Neoplastic Stem Cells, MESH: Cell Separation, MESH: Male, MESH: Glioma, glioma, MESH: Survival Analysis, MESH: Child, MESH: Brain Neoplasms, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, TP53, pilocytic astrocytoma, MESH: Female, ganglioglioma
Abstract

International audience; BACKGROUND: Primitive brain tumors are the leading cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined. METHODOLOGY/PRINCIPAL FINDINGS: Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). Most high-grade glioma-derived oncospheres (10/12) sustained long-term self-renewal akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumors. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P = 0.05, chi-square test). Survival analysis of the cohort showed an association between isolation of cells with long-term self-renewal abilities and a higher patient mortality rate (P = 0.013, log-rank test). Sampling of low- and high-grade glioma cultures showed that self-renewing cells forming oncospheres shared a molecular profile comprising embryonic and neural stem cell markers. Further characterization performed on subsets of high-grade gliomas and one low-grade glioma culture showed combination of this profile with mesenchymal markers, the radio-chemoresistance of the cells and the formation of aggressive tumors after intracerebral grafting. CONCLUSIONS/SIGNIFICANCE: In brain tumors affecting adult patients, TSCs have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors.

Published
2011
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13. Clinical epidemiology for childhood primary central nervous system tumors

Author

Bauchet, Luc, Rigau, Valérie, Mathieu-Daudé, Hélène, Fabbro-Peray, Pascale, Palenzuela, Gilles, Figarella-Branger, Dominique, Moritz, Jorge, Puget, Stéphanie, Bauchet, Fabienne, Pallusseau, Lorelei, Duffau, Hugues, Coubes, Philippe, Trétarre, Brigitte, Labrousse, François, Dhellemmes, Patrick, Neurochirurgie Pédiatrique, Société Française De, Neurochirurgie, Société Française De, Neuropathologie, Société Française De, Neuro-Oncologues D'Expression Française, Association Des, Neurochirurgie [Hôpital Gui de Chauliac], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de pathologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'épidémiologie, Groupe de neuro-oncologie du Languedoc Roussillon, Registre des Tumeurs de l'Hérault, Service de biostatistiques, Institut Universitaire de Recherche Clinique, Service de pédiatrie, Hôpital de Béziers, Service de pathologie et neuropathologie, CHU Marseille, Service de neurochirurgie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Limoges], CHU Limoges, Service de neurochirurgie pédiatrique, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hamel, Christian, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac, Université Montpellier 2 - Sciences et Techniques ( UM2 ) -IFR76-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille )

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Pediatrics, Neurology, Adolescent, Brain tumor, Neuropathology, Central Nervous System Neoplasms, Meningioma, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, Humans, Registries, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Child, business.industry, Infant, Newborn, Infant, medicine.disease, Craniopharyngioma, 3. Good health, Surgery, Oncology, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Child, Preschool, 030220 oncology & carcinogenesis, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], France, Neurology (clinical), Germ cell tumors, Neurosurgery, business, 030217 neurology & neurosurgery
Abstract

International audience; This work was conducted by the French Brain Tumor Data Bank (FBTDB) and aims to prospectively record all primary central nervous system tumors (PCNST), in France, for which histological diagnosis is available. Results concerning children are presented. This study analyzes the childhood cases (0-19 years) of newly diagnosed and histologically confirmed PCNST (during the years 2004-2006) which have been recorded by the FBTDB. All French neuropathology and neurosurgery departments participated in this program. Neurosurgeons and neuropathologists completed a data file containing socio-demographic, clinical, radiologic and anatomopathologic information. The Tumor Registry from Herault was authorized to compile the data files with personal identifiers. About 1,017 cases (533 boys and 484 girls) of newly diagnosed childhood PCNST have been recorded (gliomas: 52%, all other neuroepithelial tumors: 31%, craniopharyngioma: 5%, germ cell tumors, meningioma and neurinoma: approximately 3% each, all histological subtypes have been detailed). Tumor resections were performed in 83.3%, and biopsies in 16.7%. The distributions by histology, cryopreservation of the samples, age, sex, tumor site and surgery have been detailed. To our knowledge, this work is the first databank in Europe dedicated to PCNST that includes the collection of clinical, radiological and histological data (including cryopreservation of the specimen). The long term goals of the FBTDB are to create a national registry and a network to perform epidemiological studies, to implement clinical and basic research protocols, and to evaluate and harmonize the healthcare of children and adult patients affected by PCNST.

Published
2009
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14. Factors related to pregnancy and birth and the risk of childhood brain tumours: The ESTELLE and ESCALE studies (SFCE, France).

Author

Bailey, Helen D., Rios, Paula, Lacour, Brigitte, Guerrini‐Rousseau, Léa, Bertozzi, Anne‐Isabelle, Leblond, Pierre, Faure‐Conter, Cécile, Pellier, Isabelle, Freycon, Claire, Michon, Jean, Puget, Stéphanie, Ducassou, Stéphane, Orsi, Laurent, and Clavel, Jacqueline

Abstract

Little is known of the causes of childhood brain tumors (CBT). The aims of this study were to investigate whether extremes of birth weight were associated with increased risk of CBT and whether maternal preconceptional folic acid supplementation or breastfeeding reduced the risk. In addition, other maternal characteristics and birth related factors were also investigated. We pooled data from two French national population-based case-control studies with similar designs conducted in 2003-2004 and 2010-2011. The mothers of 510 CBT cases (directly recruited from the national childhood cancer register) and 3,102 controls aged under 15 years, frequency matched by age and gender did a telephone interview, which focussed on demographic and perinatal characteristics, and maternal life style habits and reproductive history. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusted for age, sex, study of origin and relevant confounders. No association was found between CBT and birth weight or fetal growth. The use of preconceptional folic acid supplementation was rare (5.3% in cases and 7.8% in controls) and the OR was 0.8 (95% CI 0.5, 1.4). There was no association with breastfeeding, even prolonged (six months or more; OR 1.0, 95% CI 0.8, 1.4). Neither was there any association between CBT and other investigated factors (maternal body mass index, gestational weight gain, congenital abnormality, maternal reproductive history or use of fertility treatments. Although large, this study was underpowered for subtype analyses. Pooling data with other population-based studies may provide further insight into findings by CBT subtypes. [ABSTRACT FROM AUTHOR]

Published
2017
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