Unveiling the mysteries of extrachromosomal circular DNA: from generation to clinical relevance in human cancers and health

Extrachromosomal circular DNAs (eccDNAs) are a type of circular DNAs originating from but independent of chromosomal DNAs. Nowadays, with the rapid development of sequencing and bioinformatics, the accuracy of eccDNAs detection has significantly improved. This advancement has consequently enhanced the feasibility of exploring the biological characteristics and functions of eccDNAs. This review elucidates the potential mechanisms of eccDNA generation, the existing methods for their detection and analysis, and their basic features. Furthermore, it focuses on the biological functions of eccDNAs in regulating gene expression under both physiological and pathological conditions. Additionally, the review summarizes the clinical implications of eccDNAs in human cancers and health.