ISSN: 1449-2288International Journal of Biological Sciences
Global reach, higher impact
Int J Biol Sci 2022; 18(10):4006-4025. doi:10.7150/ijbs.73479 This issue Cite
Review
Pioneering insights of extrachromosomal DNA (ecDNA) generation, action and its implications for cancer therapy
Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Tianjin, 300052, P.R. China.
* These authors contributed equally.
Abstract
Extrachromosomal DNA (ecDNA) is a cancer-specific circular DNA molecule that is derived from chromosomes. In contrast with linear chromosomes, ecDNA exhibits a unique structure that can be representative of high chromosome accessibility, contributing to hyperactivated proto-oncogenes and malignant behaviours. Meanwhile, nonchromosomal inheritance and recurrent mutations of ecDNA fuel tumour heterogeneity and evolution. Recent studies have demonstrated that ecDNA drives tumorigenesis and progression and is related to poor clinical outcomes and drug resistance across widespread cancers. Although ecDNA was first observed in 1965, with technological advancements, its critical functions in tumorigenesis are currently coming forth. In this review, we summarize the current understanding of the origin, biogenesis process, discovery history, molecular mechanisms, and physiological functions of ecDNAs in cancer. Additionally, we highlight the effective research methods to study ecDNA and offer novel insights for ecDNA-directed therapies.
Keywords: extrachromosomal DNA (ecDNA), cancer, oncogene amplification, function of ecDNA, tumour evolution, intratumoural heterogeneity
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