Li Ruomeng, Wang Ying, Li Jing, Zhou Xikun
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, PR China.
Biomark Res. 2022 Jul 26;10(1):53. doi: 10.1186/s40364-022-00399-9.
Extrachromosomal circular DNA (eccDNA) is defined as a type of circular DNA that exists widely in nature and is independent of chromosomes. EccDNA has attracted the attention of researchers due to its broad, random distribution, complex biogenesis and tumor-relevant functions. EccDNA can carry complete gene information, especially the oncogenic driver genes that are often carried in tumors, with increased copy number and high transcriptional activity. The high overexpression of oncogenes by eccDNA leads to malignant growth of tumors. Regardless, the exact generation and functional mechanisms of eccDNA in disease progression are not yet clear. There is, however, an emerging body of evidence characterizing that eccDNA can be generated from multiple pathways, including DNA damage repair pathways, breakage-fusion-bridge (BFB) mechanisms, chromothripsis and cell apoptosis, and participates in the regulation of tumor progression with multiplex functions. This up-to-date review summarizes and discusses the origins, biogenesis and functions of eccDNA, including its contribution to the formation of oncogene instability and mutations, the heterogeneity and cellular senescence of tumor cells, and the proinflammatory response of tumors. We highlight the possible cancer-related applications of eccDNA, such as its potential use in the diagnosis, targeted therapy and prognostic assessment of cancer.
染色体外环状DNA（eccDNA）被定义为一种广泛存在于自然界且独立于染色体的环状DNA。由于其广泛、随机的分布、复杂的生物发生过程以及与肿瘤相关的功能，eccDNA已引起研究人员的关注。eccDNA能够携带完整的基因信息，尤其是肿瘤中常携带的致癌驱动基因，其拷贝数增加且转录活性高。eccDNA导致癌基因的高度过表达，进而引发肿瘤的恶性生长。尽管如此，eccDNA在疾病进展中的确切产生和功能机制尚不清楚。然而，越来越多的证据表明，eccDNA可通过多种途径产生，包括DNA损伤修复途径、断裂-融合-桥接（BFB）机制、染色体碎裂和细胞凋亡，并通过多种功能参与肿瘤进展的调控。这篇最新综述总结并讨论了eccDNA的起源、生物发生过程和功能，包括其对癌基因不稳定性和突变形成、肿瘤细胞异质性和细胞衰老以及肿瘤促炎反应的贡献。我们强调了eccDNA在癌症相关方面可能的应用，例如其在癌症诊断、靶向治疗和预后评估中的潜在用途。
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