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A pan-cancer compendium of chromosomal instability

Author

Listed:
  • Ruben M. Drews

    (Cancer Research UK Cambridge Institute)

  • Barbara Hernando

    (Spanish National Cancer Research Centre (CNIO))

  • Maxime Tarabichi

    (The Francis Crick Institute
    Université Libre de Bruxelles)

  • Kerstin Haase

    (The Francis Crick Institute
    Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin)

  • Tom Lesluyes

    (The Francis Crick Institute)

  • Philip S. Smith

    (Cancer Research UK Cambridge Institute)

  • Lena Morrill Gavarró

    (Cancer Research UK Cambridge Institute)

  • Dominique-Laurent Couturier

    (Cancer Research UK Cambridge Institute
    Medical Research Council Biostatistics Unit)

  • Lydia Liu

    (The Francis Crick Institute
    University of Toronto)

  • Michael Schneider

    (Cancer Research UK Cambridge Institute)

  • James D. Brenton

    (Cancer Research UK Cambridge Institute
    Addenbrooke’s Hospital
    University of Cambridge)

  • Peter Van Loo

    (The Francis Crick Institute)

  • Geoff Macintyre

    (Cancer Research UK Cambridge Institute
    Spanish National Cancer Research Centre (CNIO))

  • Florian Markowetz

    (Cancer Research UK Cambridge Institute)

Abstract

Chromosomal instability (CIN) results in the accumulation of large-scale losses, gains and rearrangements of DNA1. The broad genomic complexity caused by CIN is a hallmark of cancer2; however, there is no systematic framework to measure different types of CIN and their effect on clinical phenotypes pan-cancer. Here we evaluate the extent, diversity and origin of CIN across 7,880 tumours representing 33 cancer types. We present a compendium of 17 copy number signatures that characterize 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, which is 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.

Suggested Citation

  • 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. Br, 2022. "A pan-cancer compendium of chromosomal instability," Nature, Nature, vol. 606(7916), pages 976-983, June.
    • Handle: RePEc:nat:nature:v:606:y:2022:i:7916:d:10.1038_s41586-022-04789-9
    DOI: 10.1038/s41586-022-04789-9
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    Cited by:

    1. Carolin M. Sauer & James A. Hall & Dominique-Laurent Couturier & Thomas Bradley & Anna M. Piskorz & Jacob Griffiths & Ashley Sawle & Matthew D. Eldridge & Philip Smith & Karen Hosking & Marika A. V. R, 2023. "Molecular landscape and functional characterization of centrosome amplification in ovarian cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Philip Smith & Thomas Bradley & Lena Morrill Gavarró & Teodora Goranova & Darren P. Ennis & Hasan B. Mirza & Dilrini Silva & Anna M. Piskorz & Carolin M. Sauer & Sarwah Al-Khalidi & Ionut-Gabriel Funi, 2023. "The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Hongyu Shi & Marc J. Williams & Gryte Satas & Adam C. Weiner & Andrew McPherson & Sohrab P. Shah, 2024. "Allele-specific transcriptional effects of subclonal copy number alterations enable genotype-phenotype mapping in cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Luisa Statello & José Miguel Fernandez-Justel & Jovanna González & Marta Montes & Alessia Ranieri & Enrique Goñi & Aina M. Mas & Maite Huarte, 2024. "The chromatin-associated lncREST ensures effective replication stress response by promoting the assembly of fork signaling factors," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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