首页 > 人全基因组测序 > 《Nature Genetics》-14种肿瘤非编码区体细胞突变系统性研究-TERT Promotor
2015
01-20

《Nature Genetics》-14种肿瘤非编码区体细胞突变系统性研究-TERT Promotor

 

Systematic analysis of noncoding somatic mutations and gene expression alterations across 14 tumor types

Abstract

Somatic mutations in noncoding sequences are poorly explored in cancer, a rare exception being the recent identification of activating mutations in TERT regulatory DNA. Although this finding is suggestive of a general mechanism for oncogene activation, this hypothesis remains untested. Here we map somatic mutations in 505 tumor genomes across 14 cancer types and systematically screen for associations between mutations in regulatory regions and RNA-level changes. We identify recurrent promoter mutations in several genes but find that TERT mutations are exceptional in showing a strong and genome-wide significant association with increased expression. Detailed analysis of TERT across cancers shows that the strength of this association is highly variable and is strongest in copy number–stable cancers such as thyroid carcinoma. We additionally propose that TERT promoter mutations control expression of the nearby gene CLPTM1L. Our analysis provides a detailed pan-cancer view of TERT transcriptional activation but finds no clear evidence for frequent oncogenic promoter mutations beyond TERT.

http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3141.html

利用TCGA的14种肿瘤基因组数据,对其非编码区变异(SNV及CNV)与RNA水平表达丰度进行关联研究。下图统计了14种肿瘤基因组水平体细胞突变的中位数,有参考价值。

somatic

这篇文章其实在基因组水平并没有发现新玩意,最后也还是发现TERT这个基因的启动子突变会影响相应基因的表达。如下图,在PAN-Cancer水平,TERT启动子突变会提高该原癌基因的表达量。但是,2013年已经有两篇Science,一篇NC,发现了这个问题,不算新观点。本文系统性研究了这个问题,此外,发现TERT启动子对CLPTM1L这个基因的表达也有影响。其他noval基因启动突变的关联可信度不高。非常疑惑,按照本文的广谱筛选的思路,不应该只有TERT这一个基因这么显著吧。一是说明这个基因非常重要,个案?;二是说明其他非编码区变异是否有更重要的调控机制尚未发现。pan-cancer

 

 

 


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