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.

^{染色体不稳定性 (CIN) 导致 DNA 1}的大规模损失、增益和重排的积累。CIN 引起的广泛基因组复杂性是癌症的标志²; 然而，没有系统的框架来衡量不同类型的 CIN 及其对泛癌临床表型的影响。在这里，我们评估了代表 33 种癌症类型的 7,880 个肿瘤中 CIN 的范围、多样性和起源。我们提出了一个包含 17 个拷贝数特征的纲要，这些特征描述了特定类型的 CIN，并具有多个独立数据源支持的假定病因。这些特征可以预测药物反应并确定新的药物靶点。我们的框架完善了对受损同源重组的理解，这是最具治疗靶向性的 CIN 类型之一。我们的研究结果阐明了人类癌症基因组复杂性的基本结构，并为指导未来的 CIN 研究提供了资源。