Substitution mutational signatures in whole-genome-sequenced cancers in the UK population.

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Zou, Xueqing 
Amarante, Tauanne Dias 
Martinez-Martinez, Andrea 
Koh, Gene Ching Chiek 

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 WGS tumor-normal matched pairs, from patients recruited via the UK National Health Service. We contrasted our results to two independent cancer WGS datasets, the International Cancer Genome Consortium (ICGC) and Hartwig Foundation, involving 18,640 WGS cancers in total. Our analyses add 40 single and 18 double substitution signatures to the current mutational signature tally. Critically, we show for each organ, that cancers have a limited number of 'common' signatures and a long tail of 'rare' signatures. We provide a practical solution for utilizing this concept of common versus rare signatures in future analyses.

Base Sequence, Cohort Studies, DNA Mutational Analysis, Humans, Mutation, Neoplasms, Population, United Kingdom
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American Association for the Advancement of Science (AAAS)
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)