Extrachromosomal DNA: An Emerging Hallmark in Human Cancer
Sihan Wu, Vineet Bafna, Howard Y Chang, Paul S Mischel, Sihan Wu, Vineet Bafna, Howard Y Chang, Paul S Mischel
Abstract
Human genes are arranged on 23 pairs of chromosomes, but in cancer, tumor-promoting genes and regulatory elements can free themselves from chromosomes and relocate to circular, extrachromosomal pieces of DNA (ecDNA). ecDNA, because of its nonchromosomal inheritance, drives high-copy-number oncogene amplification and enables tumors to evolve their genomes rapidly. Furthermore, the circular ecDNA architecture fundamentally alters gene regulation and transcription, and the higher-order organization of ecDNA contributes to tumor pathogenesis. Consequently, patients whose cancers harbor ecDNA have significantly shorter survival. Although ecDNA was first observed more than 50 years ago, its critical importance has only recently come to light. In this review, we discuss the current state of understanding of how ecDNAs form and function as well as how they contribute to drug resistance and accelerated cancer evolution.
Keywords: cancer genomics; ecDNA; extrachromosomal DNA; gene amplification; non-Mendelian inheritance; tumor evolution.
Conflict of interest statement
DISCLOSURE STATEMENT
V.B. is a cofounder, consultant, and Scientific Advisory Board member of and has equity interest in Boundless Bio, Inc. (BB) and Abterra Bio, Inc. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict-of-interest policies. H.Y.C. is a cofounder of Accent Therapeutics and BB and an advisor for 10× Genomics, Arsenal Biosciences, and Spring Discovery. P.S.M. is a cofounder of BB. He has equity in the company and serves as the chair of its Scientific Advisory Board, for which he is compensated.
Figures
Source: PubMed