The repertoire of mutational signatures in human cancer

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 () and Michael R. Stratton ()
Additional contact information
Ludmil B. Alexandrov: University of California
Jaegil Kim: Broad Institute of MIT and Harvard
Nicholas J. Haradhvala: Broad Institute of MIT and Harvard
Mi Ni Huang: Duke-NUS Medical School
Alvin Wei Tian Ng: Duke-NUS Medical School
Yang Wu: Duke-NUS Medical School
Arnoud Boot: Duke-NUS Medical School
Kyle R. Covington: Baylor College of Medicine
Dmitry A. Gordenin: National Institute of Environmental Health Sciences (NIEHS)
Erik N. Bergstrom: University of California
S. M. Ashiqul Islam: University of California
Nuria Lopez-Bigas: The Barcelona Institute of Science and Technology
Leszek J. Klimczak: National Institute of Environmental Health Sciences (NIEHS)
John R. McPherson: Duke-NUS Medical School
Sandro Morganella: Wellcome Sanger Institute
Radhakrishnan Sabarinathan: Universitat Pompeu Fabra
David A. Wheeler: Baylor College of Medicine
Ville Mustonen: University of Helsinki
Gad Getz: Broad Institute of MIT and Harvard
Steven G. Rozen: Duke-NUS Medical School
Michael R. Stratton: Wellcome Sanger Institute

Nature, 2020, vol. 578, issue 7793, 94-101

Abstract: 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 analyses3–15, 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (84)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-1943-3 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:578:y:2020:i:7793:d:10.1038_s41586-020-1943-3

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-1943-3

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().