Substitution mutational signatures in whole-genome–sequenced cancers in the UK population
Author:
Degasperi Andrea12ORCID, Zou Xueqing12ORCID, Dias Amarante Tauanne12ORCID, Martinez-Martinez Andrea12, Koh Gene Ching Chiek12ORCID, Dias João M. L.12ORCID, Heskin Laura12ORCID, Chmelova Lucia12, Rinaldi Giuseppe12ORCID, Wang Valerie Ya Wen12, Nanda Arjun S.12ORCID, Bernstein Aaron12ORCID, Momen Sophie E.12, Young Jamie12ORCID, Perez-Gil Daniel12, Memari Yasin12, Badja Cherif12ORCID, Shooter Scott12ORCID, Czarnecki Jan12, Brown Matthew A.34ORCID, Davies Helen R.12, Nik-Zainal Serena12ORCID, Ambrose J. C., Arumugam P., Bevers R., Bleda M., Boardman-Pretty F., Boustred C. R., Brittain H., Caulfield M. J., Chan G. C., Fowler T., Giess A., Hamblin A., Henderson S., Hubbard T. J. P., Jackson R., Jones L. J., Kasperaviciute D., Kayikci M., Kousathanas A., Lahnstein L., Leigh S. E. A., Leong I. U. S., Lopez F. J., Maleady-Crowe F., McEntagart M., Minneci F., Moutsianas L., Mueller M., Murugaesu N., Need A. C., O‘Donovan P., Odhams C. A., Patch C., Perez-Gil D., Pereira M. B., Pullinger J., Rahim T., Rendon A., Rogers T., Savage K., Sawant K., Scott R. H., Siddiq A., Sieghart A., Smith S. C., Sosinsky A., Stuckey A., Tanguy M., Taylor Tavares A. L., Thomas E. R. A., Thompson S. R., Tucci A., Welland M. J., Williams E., Witkowska K., Wood S. M.,
Affiliation:
1. Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK. 2. Early Cancer Institute, University of Cambridge, Cambridge CB2 0XZ, UK. 3. Genomics England, Queen Mary University of London, Dawson Hall, Charterhouse Square, London EC1M 6BQ, UK. 4. Faculty of Life Sciences and Medicine, King’s College London, London SE1 9RT, UK.
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.
Publisher
American Association for the Advancement of Science (AAAS)
Subject
Multidisciplinary
Cited by
100 articles.
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