A Guide to Extrachromosomal DNA: Cancer’s Dynamic Circular Genome

Abstract Focal amplifications of oncogenes are important cancer drivers. They can occur on chromosomes or in the context of circular extrachromosomal DNA (ecDNA). Many key features of ecDNAs were described in the 1960s to 1980s, including their “unstable” nature and their ability to confer drug resistance. With the benefit of new technologies, our understanding of ecDNAs has advanced dramatically in the last decade, both in breadth and in depth, including the remarkable discovery that ecDNAs are present in 17% of all cancers and are associated with worse patient outcomes. In this study, we present a guide to ecDNA tools and biology. Significance: Focal amplifications on ecDNAs are commonly found in cancer and are associated with poor patient outcomes and distinct biology. In this review, we provide a guide to ecDNA biology and available tools as well as our perspective on this rapidly evolving field.