科学家阐明引发恶性脑癌的特殊基因突变

  最近一项刊登在Nature Communications上的研究论文中，来自英国伦敦癌症研究院(The Institute of Cancer Research)的研究人员通过研究鉴别出了引发恶性脑癌的特殊基因突变，研究者表示，基因TCF12发生错误和退行性寡轴突胶质细胞瘤(anaplastic oligodendroglioma)发生直接相关，该基因在个体胚脑组织形成过程中扮演着重要角色。
  少突神经胶质瘤是一种发展加快的癌症，其在脑部和中枢神经系统的所有肿瘤中大约占5%至10%，而且该病预后较差；文章中研究者将134名脑癌患者的癌细胞DNA和健康细胞的DNA进行了遗传序列的比较，最终鉴别出了TCF12的基因突变，研究者在7.5%的退行性寡轴突胶质细胞瘤患者中鉴别出了TCF12的突变，同时还发现这种癌症的亚型进展非常迅速。
  TCF12编码的特殊蛋白会同DNA结合同时控制其它基因的表达活性，研究者发现TCF12的突变会使得蛋白并不易于DNA结合，这样就会导致其它关键基因活性的下降，其中就包括一种名为CHD1的基因，该基因和癌症扩散直接相关。
  研究者起初对51份肿瘤样本的DNA序列进行了分析，随后在额外的83份样本中又去寻找TCF12的突变，结果研究者在78%的肿瘤样本中发现了IDH1基因的突变，这就证实了此前的研究发现。揭示遗传错误如何引发退行性寡轴突胶质细胞瘤的发生或可帮助研究者及医生们开发新型个体化疗法来帮助靶向作用引发该疾病的基因突变。
  最后研究者Richard Houlston指出，如今我们计划进行全面深入的研究来寻找引发这种罕见脑瘤的所有遗传原因，目前退行性寡轴突胶质细胞瘤很难通过外科手术进行治疗，而且其对于其它形式的疗法并无反应，因此我们希望本文的研究线索可以帮助寻找新型靶向疗法来有效改善患者的生存期及生活质量。（转化医学网360zhyx.com）
  以上为转化医学网原创翻译整理，转载请注明出处和链接！
转化医学网推荐的原文摘要：

TCF12 is mutated in anaplastic oligodendroglioma
Nature Communications      doi:10.1038/ncomms8207
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 et al.
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.