TCF12 is mutated in anaplastic oligodendroglioma.
TCF12 is mutated in anaplastic oligodendroglioma.
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DOI：
10.1038/ncomms8207
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发表时间：
2015-06-12
影响因子：
16.6
通讯作者：
Houlston, Richard S.
中科院分区：
文献类型：
--
作者：
Labreche, Karim;Simeonova, Iva;Kamoun, Aurelie;Gleize, Vincent;Chubb, Daniel;Letouze, Eric;Riazalhosseini, Yasser;Dobbins, Sara E.;Elarouci, Nabila;Ducray, Francois;de Reynies, Aurelien;Zelenika, Diana;Wardell, Christopher P.;Frampton, Mathew;Saulnier, Olivier;Pastinen, Tomi;Hallout, Sabrina;Figarella-Branger, Dominique;Dehais, Caroline;Idbaih, Ahmed;Mokhtari, Karima;Delattre, Jean-Yves;Huillard, Emmanuelle;Lathrop, G. Mark;Sanson, Marc;Houlston, Richard S.
间变性少突神经胶质瘤（AO）是罕见的原发性脑肿瘤，通常无法治愈，预后不均匀，且治疗靶点很少。大多数少突胶质细胞瘤具有染色体 1p/19q 共缺失和 IDH 突变。在这里，我们通过全外显子组测序分析了 51 个 AO，识别了先前报道的 CIC 和 FUBP1 中常见的体细胞突变。我们还鉴定了 TCF12 和另外一系列 83 AO 中的复发突变。总体而言，7.5% 的 AO 发生 TCF12 突变，TCF12 编码少突胶质细胞相关转录因子。 80% 的 TCF12 突变要么位于 bHLH 结构域（该结构域对于 TCF12 作为转录因子的功能很重要），要么是导致 TCF12 该结构域截短的移码突变。我们发现这些突变会损害 TCF12 转录活性，并与更具侵袭性的肿瘤类型相关。我们的分析提供了对驱动 AO 的独特和共享途径的进一步见解。间变性少突胶质细胞瘤是罕见且无法治愈的原发性脑肿瘤，治疗选择很少。这里拉布雷什等人。进行全外显子组测序并识别转录因子 TCF12 中反复出现的突变，这些突变与侵袭性肿瘤相关。
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. Anaplastic oligodendrogliomas are rare and incurable primary brain tumours with few treatment options. Here Labreche et al. perform whole-exome sequencing and identify recurring mutations in transcription factor TCF12, which are associated with aggressive tumours.
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影响因子：
14.9
作者：
Gonzalez-Perez A;Lopez-Bigas N
通讯作者：
Lopez-Bigas N
影响因子：
48
作者：
Gonzalez-Perez A;Perez-Llamas C;Deu-Pons J;Tamborero D;Schroeder MP;Jene-Sanz A;Santos A;Lopez-Bigas N
通讯作者：
Lopez-Bigas N
影响因子：
14.9
作者：
Costello M;Pugh TJ;Fennell TJ;Stewart C;Lichtenstein L;Meldrim JC;Fostel JL;Friedrich DC;Perrin D;Dionne D;Kim S;Gabriel SB;Lander ES;Fisher S;Getz G
通讯作者：
Getz G
影响因子：
45.3
作者：
Cairncross, Gregory;Wang, Meihua;Mehta, Minesh
通讯作者：
Mehta, Minesh
影响因子：
5.8
作者：
Arnold, K;Bordoli, L;Schwede, T
通讯作者：
Schwede, T