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

Autor: Degasperi A; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Zou X; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Amarante TD; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Martinez-Martinez A; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Koh GCC; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Dias JML; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Heskin L; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Chmelova L; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Rinaldi G; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Wang VYW; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Nanda AS; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Bernstein A; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Momen SE; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Young J; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Perez-Gil D; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Memari Y; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Badja C; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Shooter S; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Czarnecki J; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Brown MA; Genomics England, Queen Mary University of London, Dawson Hall, Charterhouse Square, London, EC1M 6BQ, UK.; Faculty of Life Sciences and Medicine, King's College London, London SE19RT, UK., Davies HR; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK., Nik-Zainal S; Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2022 Apr 22; Vol. 376 (6591). Date of Electronic Publication: 2022 Apr 22 (Print Publication: 2022).
DOI: 10.1126/science.abl9283
Abstrakt: 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.
Competing Interests: Competing interests: AD, XZ, HRD and SNZ hold patents or have submitted applications on clinical algorithms of mutational signatures (MMRDetect (number pending), HRDetect: PCT/EP2017/060294, Clinical use of signatures: PCT/EP2017/060289, Rearrangement sigantures methods: PCT/EP2017/060279, Clinical predictor: PCT/EP2017/060298, Hotspots for chromosomal rearrangements: PCT/EP2017/060298) and during this project, served advisory roles for AstraZeneca, Artios Pharma and the Scottish Genomes Project.
Databáze: MEDLINE
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