哈佛医学院Shamil R. Sunyaev、Eliezer M. Van Allen和Felix Dietlein研究小组合作，基于核苷酸背景鉴定了癌症驱动基因。该研究于2020年2月3日在线发表于国际学术期刊《自然-遗传学》杂志。
研究人员观察到，来源于被冗余突变特征性围绕环境下的突变为驱动基因的突变提供了有利于信号。因此，研究人员开发了一种将该特征与传统上用于驱动基因识别信号相结合的方法。研究人员将该方法应用于来自11873个正常肿瘤对的全外显子组测序数据，并鉴定了460个驱动基因，这些基因分布在21种与癌症相关的途径中。
该研究提供了包含28种肿瘤类型的驱动基因资源库，并依据异常核苷酸情况下的突变鉴定了其他驱动基因。
研究人员表示，癌症基因组包含大量的体细胞突变，但是这些突变很少促进肿瘤的发展。当前的方法或基于突变的复发，或通过使用生物信息学评分来近似非同义突变功能的后果来识别癌症驱动基因。冗余突变在特定核苷酸环境中富集，而驱动突变发生在功能基因，而该功能位置不一定被特定核苷酸环境所包围。
附：英文原文
Title: Identification of cancer driver genes based on nucleotide context
Author: Felix Dietlein, Donate Weghorn, Amaro Taylor-Weiner, Andr Richters, Brendan Reardon, David Liu, Eric S. Lander, Eliezer M. Van Allen, Shamil R. Sunyaev
Issue&Volume: 2020-02-03
Abstract: Cancer genomes contain large numbers of somatic mutations but few of these mutations drive tumor development. Current approaches either identify driver genes on the basis of mutational recurrence or approximate the functional consequences of nonsynonymous mutations by using bioinformatic scores. Passenger mutations are enriched in characteristic nucleotide contexts, whereas driver mutations occur in functional positions, which are not necessarily surrounded by a particular nucleotide context. We observed that mutations in contexts that deviate from the characteristic contexts around passenger mutations provide a signal in favor of driver genes. We therefore developed a method that combines this feature with the signals traditionally used for driver-gene identification. We applied our method to whole-exome sequencing data from 11,873 tumor–normal pairs and identified 460 driver genes that clustered into 21 cancer-related pathways. Our study provides a resource of driver genes across 28 tumor types with additional driver genes identified according to mutations in unusual nucleotide contexts.
DOI: 10.1038/s41588-019-0572-y
Source: https://www.nature.com/articles/s41588-019-0572-y
Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex
本期文章：《自然—遗传学》：Online/在线发表
