Åke Borg
Principal investigator
The repertoire of mutational signatures in human cancer
Author
Other contributions
- Åke Borg
- Markus Ringnér
- Johan Staaf
Summary, in English
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.
Department/s
- LUCC: Lund University Cancer Centre
- Familial Breast Cancer
- Breastcancer-genetics
- Molecular Cell Biology
- Breast/lungcancer
- Division of Translational Cancer Research
- Research Group Lung Cancer
Publishing year
2020-02
Language
English
Pages
94-101
Publication/Series
Nature
Volume
578
Issue
7793
Document type
Journal article
Publisher
Nature Publishing Group
Topic
- Medical Genetics
Keywords
- Age Factors
- Base Sequence
- Exome/genetics
- Genome, Human/genetics
- Humans
- Mutation/genetics
- Neoplasms/genetics
- Sequence Analysis, DNA
Status
Published
Research group
- Familial Breast Cancer
- Research Group Lung Cancer
ISBN/ISSN/Other
- ISSN: 0028-0836