Extrachromosomal DNA (ecDNA) amplification is an important driver alteration in cancer. It has been observed in most cancer types and is associated with worse patient outcome. The functional impact of ecDNA has been linked to its unique properties, such as its circular structure that is associated with altered chromatinization and epigenetic regulatory landscape, as well as its ability to randomly segregate during cell division, which fuels intercellular copy number heterogeneity. Recent investigations suggest that ecDNA is structurally more complex than previously anticipated and that it localizes to specialized nuclear bodies (hubs) and can act in trans as an enhancer for genes on other ecDNAs or chromosomes. In this Review, we synthesize what is currently known about how ecDNA is generated and how its genetic and epigenetic architecture affects proto-oncogene deregulation in cancer. We discuss how recently identified ecDNA functions may impact oncogenesis but also serve as new therapeutic vulnerabilities in cancer.

染色体外 DNA (ecDNA) 扩增是癌症的重要驱动因素。在大多数癌症类型中都观察到了这种情况，并且与较差的患者预后相关。 ecDNA 的功能影响与其独特的特性有关，例如其与染色质化和表观遗传调控景观改变相关的圆形结构，以及其在细胞分裂过程中随机分离的能力，这加剧了细胞间拷贝数异质性。最近的研究表明，ecDNA 在结构上比之前预期的更加复杂，并且它定位于专门的核体（中心），并且可以反式充当其他 ecDNA 或染色体上的基因的增强子。在这篇综述中，我们综合了目前已知的关于 ecDNA 如何生成以及其遗传和表观遗传结构如何影响癌症中原癌基因失调的信息。我们讨论了最近发现的 ecDNA 功能如何影响肿瘤发生，同时也作为癌症的新治疗漏洞。