1. Clinico-pathological and epigenetic heterogeneity of diffuse gliomas with FGFR3::TACC3 fusion
- Author
-
Métais, Alice, Tauziède-Espariat, Arnault, Garcia, Jeremy, Appay, Romain, Uro-Coste, Emmanuelle, Meyronet, David, Maurage, Claude Alain, Vandenbos, Fanny Burel, Rigau, Valérie, Chiforeanu, Dan Christian, Pallud, Johan, Senova, Suhan, Saffroy, Raphaël, Colin, Carole, Edjlali, Myriam, Varlet, Pascale, Figarella-Branger, Dominique F., GHU Paris Psychiatrie et Neurosciences, Hôpital Sainte-Anne [Paris], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL), 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), CHU Lille, Hôpital Pasteur [Nice] (CHU), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Pontchaillou, Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Hôpital Paul Brousse, Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), AP-HM Tumour Bank, (AC2018-31053, CRB BB-0033-00097), Association pour le Recherche sur les Tumeurs Cérébrales, Enfants Cancers Santé, French Ministry of Research, (AC-2019-3465), GIRCI Méditerranée, Imagine For Margo Association, Karen Silva, (BB-0033-00046), Liv & Lumière, clinicoPathologique pour les cancers rares du système nerveux central, Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'Adolescent, SFCE, Canceropôle PACA, Institut National Du Cancer, INCa, (2019-29), and Biopathology RENOCLIP-LOC network: A Rousseau, C Godfraind, G Gauchotte, K Mokhtari, F Bielle, F Escande, F Fina
- Subjects
DNA-methylation profiling ,FGFR3:TACC3 fusion ,Pediatric low grade glioma ,2021 WHO classification of CNS tumours ,[SDV]Life Sciences [q-bio] ,Glioblastoma - Abstract
International audience; Background: Gliomas with FGFR3::TACC3 fusion mainly occur in adults, display pathological features of glioblastomas (GB) and are usually classified as glioblastoma, IDH-wildtype. However, cases demonstrating pathological features of low-grade glioma (LGG) lead to difficulties in classification and clinical management. We report a series of 8 GB and 14 LGG with FGFR3:TACC3 fusion in order to better characterize them. Methods: Centralized pathological examination, search for TERT promoter mutation and DNA-methylation profiling were performed in all cases. Search for prognostic factors was done by the Kaplan–Meir method. Results: TERT promoter mutation was recorded in all GB and 6/14 LGG. Among the 7 cases with a methylation score > 0.9 in the classifier (v12.5), 2 were classified as glioblastoma, 4 as ganglioglioma (GG) and 1 as dysembryoplastic neuroepithelial tumor (DNET). t-SNE analysis showed that the 22 cases clustered into three groups: one included 12 cases close to glioblastoma, IDH-wildtype methylation class (MC), 5 cases each clustered with GG or DNET MC but none with PLNTY MC. Unsupervised clustering analysis revealed four groups, two of them being clearly distinct: 5 cases shared age (< 40), pathological features of LGG, lack of TERT promoter mutation, FGFR3(Exon 17)::TACC3(Exon 10) fusion type and LGG MC. In contrast, 4 cases shared age (> 40), pathological features of glioblastoma, and were TERT-mutated. Relevant factors associated with a better prognosis were age < 40 and lack of TERT promoter mutation. Conclusion: Among gliomas with FGFR3::TACC3 fusion, age, TERT promoter mutation, pathological features, DNA-methylation profiling and fusion subtype are of interest to determine patients’ risk.
- Published
- 2023