EGAGenomicsMarc Sansonhttps://ega-archive.org/dacs/EGAC00001000328EGAEGA DAC EGAC00001000328EGAmarc.sanson@psl.aphp.frAnaplastic 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.TCF12 is mutated in anaplastic oligodendroglioma.Labreche Karim K, Simeonova Iva I, Kamoun Aurélie A, Gleize Vincent V, Chubb Daniel D, Letouzé Eric E, Riazalhosseini Yasser Y, Dobbins Sara E SE, Elarouci Nabila N, Ducray Francois F, de Reyniès Aurélien A, Zelenika Diana D, Wardell Christopher P CP, Frampton Mathew M, Saulnier Olivier O, Pastinen Tomi T, Hallout Sabrina S, Figarella-Branger Dominique D, Dehais Caroline C, Idbaih Ahmed A, Mokhtari Karima K, Delattre Jean-Yves JY, Huillard Emmanuelle E, Mark Lathrop G G, Sanson Marc M, Houlston Richard S RSWell Differentiated Oligodendroglioma, WHO grade III oligodendroglial neoplasm, oligodendroglioma, Oligodendroglioma-Ependymoma, ALF1, malignant, undifferentiated oligodendroglioma, Mixed Oligodendroglioma Ependymoma, Anaplastic Oligodendrogliomas, Mixed Oligodendroglioma-Astrocytoma, ME1, Well-Differentiated Oligodendrogliomas, HTF4, Anaplastic, Oligodendroglioma-Ependymomas, Childhood Oligodendroglioma, Well-Differentiated, Well-Differentiated Oligodendroglioma, malignant oligodendroglioma, anaplastic oligodendroglioma, Adult Oligodendrogliomas, Mixed Oligodendroglioma-Astrocytomas, A130037E08Rik, Mixed, Oligodendroglioma-Astrocytoma, Well Differentiated, Oligodendroblastomas, WHO grade III oligodendroglial tumour, Childhood Oligodendrogliomas, Mixed Oligodendroglioma-Ependymoma, HsT17266, HEBAlt, Mixed Oligodendroglioma Astrocytoma, Oligodendroblastoma, SCBPA, anaplastic, Oligodendrogliomas., Childhood, Adult, Adult Oligodendroglioma, WHO grade III oligodendroglial tumor, HEB, Oligodendroglioma-Astrocytomas, REB, bHLHb20, Oligodendroglioma, CRS3, Mixed Oligodendroglioma-Ependymomas, Anaplastic Oligodendroglioma, HTF-4, Oligodendrogliomasfbwd4, l(2)04454, DmelCG1772, DNA polalpha, Activity, CIB1, Laboratory, pol alpha, p21[dacapo], DNA pol-73, polalpha, CG5923, DNApola, cdi4, polalpha50, DmelCG7108, AAG, Pol, Mid1, MID1, 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