ecDNA within tumors: a new mechanism that drives tumor heterogeneity and drug resistance

摘要

A recent study by Hoon Kim et al. published in Nature Geneticsdemonstrated that extrachromosomal DNA (ecDNA)-based oncogeneamplification frequently occurs in most cancer types andthat it is different from chromosomal amplification.1 The authorsfurther showed that ecDNA in multiple cancer types leads to pooroutcomes in patients; thus, ecDNA is a novel potential diagnosticor therapeutic target for tumor treatment (Fig. 1).Tumor cells adopt various unique biological mechanisms todrive their aggressive behavior and ensure survival. Early studieshave documented that oncogenes amplified on extrachromosomalDNA (ecDNA) show high expression levels of mRNAtranscripts.2 The extrachromosomal gene was first described byYasuo Hoota and Alix Bassel in 1965.3 It was later named ecDNA,which is a class of circular DNA ranging from tens to millions ofbase pairs in size.4 Pan-cancer analyses revealed that oncogenesencoded on ecDNA were among the most highly expressed genesin the transcriptome of the tumors,5 suggesting that ecDNA mayplay pivotal roles in tumor progression.