Extrachromosomal DNA: drivers of tumor heterogeneity and evolution
Siwen Zhao, Enwu Xu, Jirong Jie, Chao Su, Yanyi You, Ziqing Jiang, Xiaohui Wen, Fengying Gong, Ying Lv, Ying Liu, Fei Li, Qin Fan, Daoqi ZhuAbstract
Background
Extrachromosomal DNA (ecDNA) is a key structural variant in cancer genomes, recently identified as a crucial driver of tumor heterogeneity and evolution.
Aim
This review aims to summarize the molecular characteristics of ecDNA and elucidate the mechanisms by which it influences tumor evolution and heterogeneity.
Design
Narrative review.
Methods
We conducted a literature search on the formation, function, and clinical implications of ecDNA using PubMed and other relevant databases.
Results
ecDNA is prevalent in highly invasive tumors and enhances oncogene expression by forming multifunctional transcriptional hubs. Its random mitotic distribution generates high intra-tumoral copy number heterogeneity, allowing cells to dynamically regulate oncogene expression and rapidly adapt to selective pressures.
Conclusions
ecDNA offers a novel perspective on tumor resistance mechanisms. Targeting ecDNA formation and regulatory networks holds promise for developing new combination therapies and biomarkers for malignant tumors.