Overview of ecDNA

Extrachromosomal DNA (ecDNA) is a self-replicating circular DNA, and since its discovery in 1965 in neuroblastoma cell lines, is an important driver of alteration in cancer. Recent studies demonstrate the presence of ecDNA in various malignant tumors. The functional impact of ecDNA is associated with its ability to randomly segregate during cell division, which fuels inter-cellular copy number heterogeneity and its circular structure, which is associated with altered chromatinization and epigenetic regulatory landscape as well. Recent technical advances demonstrate that ecDNA can serve as multifunctional molecules, such as epigenetic remodeling, telomere trimming, and the regulation of signaling pathways and drug resistance. Nevertheless, the underlying mechanisms and future applications of ecDNA remain to be determined. This chapter focuses on discussing the structure of ecDNA and its relevance in carcinogenesis, signaling pathways, drug resistance, clinical applications, and therapeutic modalities to target ecDNA.