title: TCF12 is mutated in anaplastic oligodendroglioma.
abstract: Anaplastic oligodendroglioma (AO) are rare primary brain tumours that are generally incurable, with heterogeneous prognosis and few treatment targets identified. Most oligodendrogliomas have chromosomes 1p/19q co-deletion and an IDH mutation. Here we analysed 51 AO by whole-exome sequencing, identifying previously reported frequent somatic mutations in CIC and FUBP1. We also identified recurrent mutations in TCF12 and in an additional series of 83 AO. Overall, 7.5% of AO are mutated for TCF12, which encodes an oligodendrocyte-related transcription factor. Eighty percent of TCF12 mutations identified were in either the bHLH domain, which is important for TCF12 function as a transcription factor, or were frameshift mutations leading to TCF12 truncated for this domain. We show that these mutations compromise TCF12 transcriptional activity and are associated with a more aggressive tumour type. Our analysis provides further insights into the unique and shared pathways driving AO.
authors.affiliation: 1] Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK [2] Inserm, U 1127, ICM, F-75013 Paris, France [3] CNRS, UMR 7225, ICM, F-75013 Paris, France [4] Institut du Cerveau et de la Moelle épinière ICM, Paris 75013, France [5] Sorbonne Universités, UPMC Université Paris 06, UMR S 1127, F-75013 Paris, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Labreche
authors.affiliation: 1] Inserm, U 1127, ICM, F-75013 Paris, France [2] CNRS, UMR 7225, ICM, F-75013 Paris, France [3] Institut du Cerveau et de la Moelle épinière ICM, Paris 75013, France [4] Sorbonne Universités, UPMC Université Paris 06, UMR S 1127, F-75013 Paris, France.
authors.forename: Iva
authors.initials: I
authors.lastname: Simeonova
authors.affiliation: Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, 75013 Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Kamoun
authors.affiliation: 1] Inserm, U 1127, ICM, F-75013 Paris, France [2] CNRS, UMR 7225, ICM, F-75013 Paris, France [3] Institut du Cerveau et de la Moelle épinière ICM, Paris 75013, France [4] Sorbonne Universités, UPMC Université Paris 06, UMR S 1127, F-75013 Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Gleize
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chubb
authors.affiliation: Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, 75013 Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Letouzé
authors.affiliation: 1] Department of Human Genetics, McGill University, Montreal, Quebec, Canada H3A 0G1 [2] McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada H3A 0G1.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Riazalhosseini
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Dobbins
authors.affiliation: Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, 75013 Paris, France.
authors.forename: Nabila
authors.initials: N
authors.lastname: Elarouci
authors.affiliation: INSERM U1028, CNRS UMR5292, Service de Neuro-oncologie, Hopital neurologique, Hospices civils de Lyon, Lyon Neuroscience Research Center, Neuro-Oncology and Neuro-Inflammation Team, 69677 Lyon, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Ducray
authors.affiliation: Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, 75013 Paris, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: de Reyniès
authors.affiliation: Centre National de Génotypage, IG/CEA, 2 rue Gaston Crémieux, CP 5721, Evry 91057, France.
authors.forename: Diana
authors.initials: D
authors.lastname: Zelenika
authors.affiliation: Division of Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Wardell
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Mathew
authors.initials: M
authors.lastname: Frampton
authors.affiliation: 1] Inserm, U 1127, ICM, F-75013 Paris, France [2] CNRS, UMR 7225, ICM, F-75013 Paris, France [3] Institut du Cerveau et de la Moelle épinière ICM, Paris 75013, France [4] Sorbonne Universités, UPMC Université Paris 06, UMR S 1127, F-75013 Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Saulnier
authors.affiliation: 1] Department of Human Genetics, McGill University, Montreal, Quebec, Canada H3A 0G1 [2] McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada H3A 0G1.
authors.forename: Tomi
authors.initials: T
authors.lastname: Pastinen
authors.affiliation: 1] Inserm, U 1127, ICM, F-75013 Paris, France [2] CNRS, UMR 7225, ICM, F-75013 Paris, France [3] Institut du Cerveau et de la Moelle épinière ICM, Paris 75013, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Hallout
authors.affiliation: 1] AP-HM, Hôpital de la Timone, Service d'anatomie pathologique et de neuropathologie, 13385 Marseille, France [2] Université de la Méditerranée, Aix-Marseille, Faculté de Médecine La Timone, CRO2, UMR 911 Marseille, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de neurologie 2-Mazarin, 75013 Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dehais
authors.affiliation: 1] Inserm, U 1127, ICM, F-75013 Paris, France [2] CNRS, UMR 7225, ICM, F-75013 Paris, France [3] Institut du Cerveau et de la Moelle épinière ICM, Paris 75013, France [4] Sorbonne Universités, UPMC Université Paris 06, UMR S 1127, F-75013 Paris, France [5] AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de neurologie 2-Mazarin, 75013 Paris, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Idbaih
authors.affiliation: 1] Inserm, U 1127, ICM, F-75013 Paris, France [2] CNRS, UMR 7225, ICM, F-75013 Paris, France [3] Institut du Cerveau et de la Moelle épinière ICM, Paris 75013, France [4] AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire de Neuropathologie R. Escourolle, 75013 Paris, France.
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.affiliation: 1] Inserm, U 1127, ICM, F-75013 Paris, France [2] CNRS, UMR 7225, ICM, F-75013 Paris, France [3] Institut du Cerveau et de la Moelle épinière ICM, Paris 75013, France [4] Sorbonne Universités, UPMC Université Paris 06, UMR S 1127, F-75013 Paris, France [5] AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de neurologie 2-Mazarin, 75013 Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
authors.affiliation: 1] Inserm, U 1127, ICM, F-75013 Paris, France [2] CNRS, UMR 7225, ICM, F-75013 Paris, France [3] Institut du Cerveau et de la Moelle épinière ICM, Paris 75013, France [4] Sorbonne Universités, UPMC Université Paris 06, UMR S 1127, F-75013 Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Huillard
authors.affiliation: 1] Department of Human Genetics, McGill University, Montreal, Quebec, Canada H3A 0G1 [2] McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada H3A 0G1.
authors.forename: G
authors.initials: G
authors.lastname: Mark Lathrop
authors.affiliation: 1] Inserm, U 1127, ICM, F-75013 Paris, France [2] CNRS, UMR 7225, ICM, F-75013 Paris, France [3] Institut du Cerveau et de la Moelle épinière ICM, Paris 75013, France [4] Sorbonne Universités, UPMC Université Paris 06, UMR S 1127, F-75013 Paris, France [5] AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de neurologie 2-Mazarin, 75013 Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics*; D015536:Down-Regulation; D006801:Humans; D009154:Mutation; D009837:Oligodendroglioma / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C073366:TCF12 protein, human