DNA damage

Archaeology

Genome instability

Chromosomal fragile site

Bioinformatics

Biology

History

Homologous recombination

Gene

Cancer

Chromosome instability

Compendium

Computational biology

Chromosome

Genetics

Nature

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. Copy number signatures characterize different types of chromosomal instability&nbsp;and predict drug response.

A pan-cancer compendium of chromosomal instability