Substitution mutational signatures in whole-genome–sequenced cancers in the UK population
Authors
Publication Date
2022-04-22Journal Title
Science
ISSN
0036-8075
Publisher
American Association for the Advancement of Science
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Nik-Zainal, S. (2022). Substitution mutational signatures in whole-genome–sequenced cancers in the UK population. Science https://doi.org/10.1126/science.abl9283
Abstract
Whole-genome sequencing (WGS) permits comprehensive cancer genome analyses, revealing mutational signatures, imprints of DNA damage, and repair processes that have arisen in each patient’s cancer. We performed mutational signature analyses on 12,222 whole-genome–sequenced tumor-normal matched pairs from patients recruited via the UK National Health Service (NHS). We contrasted our results with two independent cancer WGS datasets—from the International Cancer Genome Consortium (ICGC) and the Hartwig Medical Foundation (HMF)—involving 18,640 whole-genome–sequenced cancers in total. Our analyses add 40 single and 18 double substitution signatures to the current mutational signature tally. We show for each organ that cancers have a limited number of common signatures and a
long tail of rare signatures, and we provide a practical solution for applying this concept of common versus rare signatures to future analyses.
Sponsorship
Cancer Research UK (23916)
Cancer Research UK (23433)
Cancer Research UK (C60100/A27815)
Dr. Josef Steiner Cancer Foundation (Award 2019)
Gray Foundation (via Massachusetts General Hospital) (235599)
Identifiers
External DOI: https://doi.org/10.1126/science.abl9283
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336115
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