TCF12 is mutated in anaplastic oligodendroglioma

Karim Labreche, Iva Simeonova, Aurélie Kamoun, Vincent Gleize, Daniel Chubb, Eric Letouzé, Yasser Riazalhosseini, Sara E. Dobbins, Nabila Elarouci, Francois Ducray, Aurélien de Reyniès, Diana Zelenika, Christopher P. Wardell, Mathew Frampton, Olivier Saulnier, Tomi Pastinen, Sabrina Hallout, Dominique Figarella-Branger, Caroline Dehais, Ahmed Idbaih, Karima Mokhtari, Jean-Yves Delattre, Emmanuelle Huillard, G. Mark Lathrop, Marc Sanson and Richard S. Houlston ()
Additional contact information
Karim Labreche: The Institute of Cancer Research
Iva Simeonova: Inserm, U 1127, ICM
Aurélie Kamoun: Programme Cartes d’Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer
Vincent Gleize: Inserm, U 1127, ICM
Daniel Chubb: The Institute of Cancer Research
Eric Letouzé: Programme Cartes d’Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer
Yasser Riazalhosseini: McGill University
Sara E. Dobbins: The Institute of Cancer Research
Nabila Elarouci: Programme Cartes d’Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer
Francois Ducray: INSERM U1028, CNRS UMR5292, Service de Neuro-oncologie, Hopital neurologique, Hospices civils de Lyon, Lyon Neuroscience Research Center, Neuro-Oncology and Neuro-Inflammation Team
Aurélien de Reyniès: Programme Cartes d’Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer
Diana Zelenika: Centre National de Génotypage
Christopher P. Wardell: The Institute of Cancer Research
Mathew Frampton: The Institute of Cancer Research
Olivier Saulnier: Inserm, U 1127, ICM
Tomi Pastinen: McGill University
Sabrina Hallout: Inserm, U 1127, ICM
Dominique Figarella-Branger: AP-HM, Hôpital de la Timone, Service d’anatomie pathologique et de neuropathologie
Caroline Dehais: AP-HP, Groupe Hospitalier Pitié-Salpêtrière
Ahmed Idbaih: Inserm, U 1127, ICM
Karima Mokhtari: Inserm, U 1127, ICM
Jean-Yves Delattre: Inserm, U 1127, ICM
Emmanuelle Huillard: Inserm, U 1127, ICM
G. Mark Lathrop: McGill University
Marc Sanson: Inserm, U 1127, ICM
Richard S. Houlston: The Institute of Cancer Research

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8207

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