Extrachromosomal oncogene amplification in tumour pathogenesis and evolution

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. The existence of extrachromosomal DNA (ecDNA) in cancer was first described decades ago, but recent reports of oncogene amplification on ecDNA have reinvigorated interest in this field. This Perspectives article discusses the potential implications of oncogene amplification on ecDNA in cancer.