Co-occurrence of histone H3 K27M and BRAF V600E mutations in paediatric midline grade I ganglioglioma
| Autor: | 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 |
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| Přispěvatelé: | 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, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | Brain Pathology Brain Pathology, 2018, ⟨10.1111/bpa.12473⟩ Brain Pathology, Wiley, 2018, ⟨10.1111/bpa.12473⟩ Brain Pathol Brain Pathology, Wiley, 2017, 〈10.1111/bpa.12473〉 |
| ISSN: | 1015-6305 1750-3639 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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