1. A pan-cancer compendium of chromosomal instability
- Author
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Ruben M. Drews, Barbara Hernando, Maxime Tarabichi, Kerstin Haase, Tom Lesluyes, Philip S. Smith, Lena Morrill Gavarró, Dominique-Laurent Couturier, Lydia Liu, Michael Schneider, James D. Brenton, Peter Van Loo, Geoff Macintyre, Florian Markowetz, Drews, Ruben M [0000-0001-7360-4970], Haase, Kerstin [0000-0002-0944-5618], Lesluyes, Tom [0000-0003-2251-5884], Smith, Philip [0000-0002-9306-1747], Morrill Gavarró, Lena [0000-0002-2242-4010], Couturier, Dominique [0000-0001-5774-5036], Liu, Lydia [0000-0001-6026-3169], Brenton, James [0000-0002-5738-6683], Van Loo, Peter [0000-0003-0292-1949], Macintyre, Geoff [0000-0003-3906-467X], Markowetz, Florian [0000-0002-2784-5308], and Apollo - University of Cambridge Repository
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Multidisciplinary ,DNA Copy Number Variations ,Chromosomal Instability ,Gene Expression Profiling ,Neoplasms ,virus diseases ,Humans ,Molecular Targeted Therapy ,urologic and male genital diseases ,Homologous Recombination ,neoplasms ,female genital diseases and pregnancy complications ,Article - Abstract
Chromosomal instability (CIN) results in the accumulation of large-scale losses, gains, and rearrangements of DNA(1). The broad genomic complexity caused by CIN is a hallmark of cancer(2), however, there is no systematic framework to measure different types of CIN and their impact on clinical phenotypes pan-cancer. Here, we evaluate the extent, diversity and origin of chromosomal instability across 7,880 tumours representing 33 cancer types. We present a compendium of 17 copy number signatures characterising specific types of CIN, with putative aetiologies supported by multiple independent data sources. The signatures predict drug response and identify new drug targets. Our framework refines the understanding of impaired homologous recombination, one of the most therapeutically targetable types of CIN. Our results illuminate a fundamental structure underlying genomic complexity in human cancers and provide a resource to guide future CIN research.
- Published
- 2022
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