文章：

人类癌症中的非编码驱动突变

Non-coding driver mutations in human cancer

原文发布日期：2021-07-06

DOI: 10.1038/s41568-021-00371-z

类型: Review Article

开放获取: 否

英文摘要：

Tumour formation involves random mutagenic events and positive evolutionary selection acting on a subset of such events, referred to as driver mutations. A decade of careful surveying of tumour DNA using exome-based analyses has revealed a multitude of protein-coding somatic driver mutations, some of which are clinically actionable. Today, a transition towards whole-genome analysis is well under way, technically enabling the discovery of potential driver mutations occurring outside protein-coding sequences. Mutations are abundant in this vast non-coding space, which is more than 50 times larger than the coding exome, but reliable identification of selection signals in non-coding DNA remains a challenge. In this Review, we discuss recent findings in the field, where the emerging landscape is one in which non-coding driver mutations appear to be relatively infrequent. Nevertheless, we highlight several notable discoveries. We consider possible reasons for the relative absence of non-coding driver events, as well as the difficulties associated with detecting signals of positive selection in non-coding DNA.

摘要翻译： 

肿瘤形成涉及随机突变事件以及对此类事件中一部分（即驱动突变）起作用的积极进化选择。基于外显子组的肿瘤DNA细致筛查研究已开展十年，揭示了大量蛋白质编码体细胞驱动突变，其中部分具有临床可行性。当前，该领域正全面转向全基因组分析，这在技术上使得发现蛋白质编码序列之外潜在驱动突变成为可能。在这片超过编码外显子组50倍规模的广阔非编码区域内，突变极为丰富，但可靠识别非编码DNA中阳性选择信号仍面临挑战。本文综述讨论了该领域最新发现，现有研究图景显示非编码驱动突变似乎相对罕见。尽管如此，我们仍重点阐述了若干值得关注的发现，并探讨了非编码驱动事件相对缺失的可能原因，以及检测非编码DNA中阳性选择信号所面临的困难。

原文链接：

Non-coding driver mutations in human cancer