Classification of extrachromosomal circular DNA with a focus on the role of extrachromosomal DNA (ecDNA) in tumor heterogeneity and progression

Abstract

Although the eukaryotic genome is mainly comprised of linear chromosomal DNA, genes can also be found outside of chromosomes. The unconventional presence of extrachromosomal genes is usually found to be circular, and these structures are named extrachromosomal circular DNA (eccDNA), which are often observed in cancer cells. Various types of eccDNA including small polydispersed DNA (spcDNA), telomeric cirlces, microDNA, etc. have been discovered. Among these eccDNA, extrachromosomal DNA (ecDNA), which encompasses the full spectrum of large, gene-containing extrachromosomal particles, has regained great research interest due to recent technological advances such as next-generation sequencing and super-resolution microscopy. In this review, we summarize the different types of eccDNA and discuss the role of eccDNA, especially ecDNA in tumor heterogeneity and progression. Additionally, we discuss some possible future investigative directions related to ecDNA biogenesis and its clinical application.

Keywords: Biogenesis; Extrachromosomal DNA; Micronuclei; Oncogene amplification; Tumor heterogeneity; eccDNA.