The Repertoire of Mutational Signatures in Human Cancer
Article The repertoire of mutational signatures in human cancer https://doi.org/10.1038/s41586-020-1943-3 Ludmil B. Alexandrov1,25, Jaegil Kim2,25, Nicholas J. Haradhvala2,3,25, Mi Ni Huang4,5,25, Alvin Wei Tian Ng4,5, Yang Wu4,5, Arnoud Boot4,5, Kyle R. Covington6,7, Dmitry A. Gordenin8, Received: 18 May 2018 Erik N. Bergstrom1, S. M. Ashiqul Islam1, Nuria Lopez-Bigas9,10,11, Leszek J. Klimczak12, Accepted: 18 November 2019 John R. McPherson4,5, Sandro Morganella13, Radhakrishnan Sabarinathan10,14,15, David A. Wheeler6,16, Ville Mustonen17,18,19, PCAWG Mutational Signatures Working Group20, Published online: 5 February 2020 Gad Getz2,3,21,22,26, Steven G. Rozen4,5,23,26*, Michael R. Stratton13,26* & PCAWG Consortium24 The number of DBSs is proportional to the number of SBSs, with few exceptions Open access 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 identifed 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 analyses3–15, 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.
[Show full text]