英国惠康桑格研究所Michael R. Stratton和新加坡国立杜克大学医学院Steven G. Rozen合作在研究中取得进展。他们探索了人类癌症的突变特征。这一研究成果在线发表在2020年2月5日的国际学术期刊《自然》上。
作为国际癌症基因组联合会（ICGC）和癌症基因组图谱（TCGA）的全基因组泛癌基因分析（PCAWG）联合会的一部分，研究人员利用了来自4,645个全基因组和19,184个外显子测序的84,729,690个体细胞突变样本来确定癌症突变的特征，这些样本涵盖大多数癌症类型。研究人员确定了49个单碱基取代、11个双碱基取代、4个簇碱基取代和17个小的插入和删除特征。与先前的分析相比，该数据集的实际大小可使研究人员发现新的特征，分离重叠的特征以及将特征码分解为可能代表相关但不同的DNA损伤、修复和/或复制机制的成分。通过估计每个特征对单个癌症基因组突变的贡献，研究人员揭示了一些与外源或内源性暴露以及缺陷性DNA维持过程相关联特征。
研究人员表示，癌症基因组中的体细胞突变是由多种突变引起的，每个突变都会产生特定的突变特征。
附：英文原文
Title: The repertoire of mutational signatures in human cancer
Author: Ludmil B. Alexandrov, Jaegil Kim, Nicholas J. Haradhvala, Mi Ni Huang, Alvin Wei Tian Ng, Yang Wu, Arnoud Boot, Kyle R. Covington, Dmitry A. Gordenin, Erik N. Bergstrom, S. M. Ashiqul Islam, Nuria Lopez-Bigas, Leszek J. Klimczak, John R. McPherson, Sandro Morganella, Radhakrishnan Sabarinathan, David A. Wheeler, Ville Mustonen, Gad Getz, Steven G. Rozen, Michael R. Stratton
Issue&Volume: 2020-02-05
Abstract: Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature1. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses3,4,5,6,7,8,9,10,11,12,13,14,15, enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated—but distinct—DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.
DOI: 10.1038/s41586-020-1943-3
Source: https://www.nature.com/articles/s41586-020-1943-3
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
