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TCF12 is mutated in anaplastic oligodendroglioma

12 juin 2015Nature Communications

DOI : 10.1038/ncomms8207

Auteurs

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, Richard S. Houlston, Clovis Adam, Marie Andraud, Marie-Hélène Aubriot-Lorton, Luc Bauchet, Patrick Beauchesne, Claire Blechet, Mario Campone, Antoine Carpentier, Catherine Carpentier, Ioana Carpiuc, Marie-Pierre Chenard, Danchristian Chiforeanu, Olivier Chinot, Elisabeth Cohen-Moyal, Philippe Colin, Phong Dam-Hieu, Christine Desenclos, Nicolas Desse, Frederic Dhermain, Marie-Danièle Diebold, Sandrine Eimer, Thierry Faillot, Mélanie Fesneau, Denys Fontaine, Stéphane Gaillard, Guillaume Gauchotte, Claude Gaultier, Francois Ghiringhelli, Joel Godard, Edouard Marcel Gueye, Jean Sebastien Guillamo, Selma Hamdi-Elouadhani, Jerome Honnorat, Jean Louis Kemeny, Toufik Khallil, Anne Jouvet, Francois Labrousse, Olivier Langlois, Annie Laquerriere, Emmanuelle Lechapt-Zalcman, Caroline Le Guérinel, Pierre-Marie Levillain, Hugues Loiseau, Delphine Loussouarn, Claude-Alain Maurage, Philippe Menei, Marie Janette Motsuo Fotso, Georges Noel, Fabrice Parker, Michel Peoc’h, Marc Polivka, Isabelle Quintin-Roué, Carole Ramirez, Damien Ricard, Pomone Richard, Valérie Rigau, Audrey Rousseau, Gwenaelle Runavot, Henri Sevestre, Marie Christine Tortel, Emmanuelle Uro-Coste, Fanny Burel-Vandenbos, Elodie Vauleon, Gabriel Viennet, Chiara Villa, Michel Wager,

Résumé

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.

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