Extrachromosomal DNA (ecDNA) has recently been recognized as a major contributor to cancer pathogenesis that is identified in most cancer types and is associated with poor outcomes. When it was discovered over 60 years ago, ecDNA was considered to be rare, and its impact on tumour biology was not well understood. The application of modern imaging and computational techniques has yielded powerful new insights into the importance of ecDNA in cancer. The non-chromosomal inheritance of ecDNA during cell division results in high oncogene copy number, intra-tumoural genetic heterogeneity and rapid tumour evolution that contributes to treatment resistance and shorter patient survival. In addition, the circular architecture of ecDNA results in altered patterns of gene regulation that drive elevated oncogene expression, potentially enabling the remodelling of tumour genomes. The generation of clusters of ecDNAs, termed ecDNA hubs, results in interactions between enhancers and promoters in trans, yielding a new paradigm in oncogenic transcription. In this Review, we highlight the rapid advancements in ecDNA research, providing new insights into ecDNA biogenesis, maintenance and transcription and its role in promoting tumour heterogeneity. To conclude, we delve into a set of unanswered questions whose answers will pave the way for the development of ecDNA targeted therapeutic approaches.

染色体外 DNA (ecDNA) 最近被认为是癌症发病机制的主要贡献者，在大多数癌症类型中都已发现，并且与不良预后相关。60 多年前被发现时，ecDNA 被认为很罕见，而且它对肿瘤生物学的影响尚不清楚。现代成像和计算技术的应用对 ecDNA 在癌症中的重要性产生了强有力的新见解。细胞分裂过程中 ecDNA 的非染色体遗传导致癌基因拷贝数高、肿瘤内遗传异质性和肿瘤快速进化，从而导致治疗耐药性和患者生存期缩短。此外，ecDNA 的环状结构会导致基因调控模式的改变，从而驱动癌基因表达升高，从而有可能实现肿瘤基因组的重塑。ecDNA 簇的产生（称为 ecDNA 中心）导致反式增强子和启动子之间的相互作用，从而产生致癌转录的新范例。在这篇综述中，我们重点介绍了 ecDNA 研究的快速进展，为 ecDNA 生物发生、维持和转录及其在促进肿瘤异质性中的作用提供了新的见解。最后，我们深入研究了一系列悬而未决的问题，这些问题的答案将为 ecDNA 靶向治疗方法的开发铺平道路。