研究揭示人類癌症的突變特徵

研究揭示人類癌症的突變特徵

作者：

小柯機器人

發布時間：2020/2/12 13:30:48

英國惠康桑格研究所Michael R. Stratton和新加坡國立杜克大學醫學院Steven G. Rozen合作在研究中取得進展。他們探索了人類癌症的突變特徵。這一研究成果在線發表在2020年2月5日的國際學術期刊《自然》上。

作為國際癌症基因組聯合會（ICGC）和癌症基因組圖譜（TCGA）的全基因組泛癌基因分析（PCAWG）聯合會的一部分，研究人員利用了來自4,645個全基因組和19,184個外顯子測序的84,729,690個體細胞突變樣本來確定癌症突變的特徵，這些樣本涵蓋大多數癌症類型。研究人員確定了49個單鹼基取代、11個雙鹼基取代、4個簇鹼基取代和17個小的插入和刪除特徵。與先前的分析相比，該數據集的實際大小可使研究人員發現新的特徵，分離重疊的特徵以及將特徵碼分解為可能代表相關但不同的DNA損傷、修復和/或複製機制的成分。通過估計每個特徵對單個癌症基因組突變的貢獻，研究人員揭示了一些與外源或內源性暴露以及缺陷性DNA維持過程相關聯特徵。

研究人員表示，癌症基因組中的體細胞突變是由多種突變引起的，每個突變都會產生特定的突變特徵。

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