The repertoire of mutational signatures in human cancer.

TitleThe repertoire of mutational signatures in human cancer.
Publication TypeJournal Article
Year of Publication2020
AuthorsAlexandrov, LB, Kim, J, Haradhvala, NJ, Huang, MNi, Ng, AWei Tian, Wu, Y, Boot, A, Covington, KR, Gordenin, DA, Bergstrom, EN, Islam, SMAshiqul, Lopez-Bigas, N, Klimczak, LJ, McPherson, JR, Morganella, S, Sabarinathan, R, Wheeler, DA, Mustonen, V, Getz, G, Rozen, SG, Stratton, MR
Corporate AuthorsPCAWG Mutational Signatures Working Group, PCAWG Consortium
Date Published2020 Feb
KeywordsAge Factors, Base Sequence, Exome, Genome, Human, Humans, Mutation, Neoplasms, Sequence Analysis, DNA

Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 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 analyses, 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.

Alternate JournalNature
PubMed ID32025018
PubMed Central IDPMC7054213
Grant ListP30 CA016672 / CA / NCI NIH HHS / United States
/ ERC_ / European Research Council / International
206194 / WT_ / Wellcome Trust / United Kingdom
U24 CA143845 / CA / NCI NIH HHS / United States
P30 CA023100 / CA / NCI NIH HHS / United States
T32 GM008313 / GM / NIGMS NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
P01 CA206978 / CA / NCI NIH HHS / United States
/ WT_ / Wellcome Trust / United Kingdom
U24 CA210999 / CA / NCI NIH HHS / United States

Similar Publications