复杂的染色体重排，称为染色体发生，在癌症中广泛存在。基于人类肿瘤的大规模 DNA 测序，最常见的复杂染色体重排类型是染色体碎裂，这是一种似乎在单一事件中获得的一条（或几条）染色体的大规模、局部和集群性重排。染色体碎裂可由有丝分裂错误引发，有丝分裂错误产生包裹单个染色体或染色体片段的微核。不稳定的微核膜的破裂使其染色质暴露于胞质核酸酶并诱导染色质破碎。在泛癌基因组分析中，多达一半的肿瘤中发现了染色体碎裂重排，它可以通过抑癌基因失活、原癌基因激活或通过产生编码癌基因的自我繁殖染色体外环状DNA或基因扩增来促进肿瘤发生。赋予抗癌药物耐药性的基因。在这里，我们讨论了对这些复杂的基因组重排及其在癌症中的影响的机制的了解。© 2023。施普林格自然有限公司。

Complex chromosome rearrangements, known as chromoanagenesis, are widespread in cancer. Based on large-scale DNA sequencing of human tumours, the most frequent type of complex chromosome rearrangement is chromothripsis, a massive, localized and clustered rearrangement of one (or a few) chromosomes seemingly acquired in a single event. Chromothripsis can be initiated by mitotic errors that produce a micronucleus encapsulating a single chromosome or chromosomal fragment. Rupture of the unstable micronuclear envelope exposes its chromatin to cytosolic nucleases and induces chromothriptic shattering. Found in up to half of tumours included in pan-cancer genomic analyses, chromothriptic rearrangements can contribute to tumorigenesis through inactivation of tumour suppressor genes, activation of proto-oncogenes, or gene amplification through the production of self-propagating extrachromosomal circular DNAs encoding oncogenes or genes conferring anticancer drug resistance. Here, we discuss what has been learned about the mechanisms that enable these complex genomic rearrangements and their consequences in cancer.© 2023. Springer Nature Limited.