Aaron Bernstein

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

Publisher: American Association for the Advancement of Science (AAAS)

Date: 22-04-2022

DOI: 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.

National Cancer Institute

Location: United States of America

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National Center For Advancing Translational Sciences

Location: United States of America

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University Of Cambridge

Location: United Kingdom of Great Britain and Northern Ireland

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National Center For Advancing Translational Sciences

Location: No location found

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University Of Cambridge

Location: No location found

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