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A pan-cancer compendium of chromosomal instability

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Hernando, Barbara 
Tarabichi, Maxime 

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.

Description

Keywords

Chromosomal Instability, Homologous Recombination, Humans, Molecular Targeted Therapy, Neoplasms

Journal Title

Nature

Conference Name

Journal ISSN

0028-0836
1476-4687

Volume Title

Publisher

Springer Science and Business Media LLC
Sponsorship
Cancer Research UK (C14303/A17197)
Cancer Research UK (A25117)
Cancer Research UK (22905)
Cancer Research UK (19274)
Cancer Research UK (11592)