The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.
Nat Rev Cancer. 2019 May;19(5):283-288. doi: 10.1038/s41568-019-0128-6.
Recent reports have demonstrated that oncogene amplification on extrachromosomal DNA (ecDNA) is a frequent event in cancer, providing new momentum to explore a phenomenon first discovered several decades ago. The direct consequence of ecDNA gains in these cases is an increase in DNA copy number of the oncogenes residing on the extrachromosomal element. A secondary effect, perhaps even more important, is that the unequal segregation of ecDNA from a parental tumour cell to offspring cells rapidly increases tumour heterogeneity, thus providing the tumour with an additional array of responses to microenvironment-induced and therapy-induced stress factors and perhaps providing an evolutionary advantage. This Perspectives article discusses the current knowledge and potential implications of oncogene amplification on ecDNA in cancer.
最近的报告表明，癌基因扩增在染色体外 DNA（ecDNA）上是癌症中的一个常见事件，为探索几十年前首次发现的现象提供了新的动力。在这些情况下，ecDNA 增益的直接后果是位于染色体外元件上的癌基因的 DNA 拷贝数增加。一个可能更重要的次要影响是，ecDNA 从亲本肿瘤细胞不均等地分配到子细胞中，迅速增加肿瘤异质性，从而为肿瘤提供了一系列对微环境诱导和治疗诱导应激因素的额外反应，并且可能提供了进化优势。本文讨论了癌基因在 ecDNA 上扩增在癌症中的当前知识和潜在影响。
