Tsiakanikas Panagiotis, Athanasopoulou Konstantina, Darioti Ioanna A, Agiassoti Vasiliki Taxiarchoula, Theocharis Stamatis, Scorilas Andreas, Adamopoulos Panagiotis G
Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece.
First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece.
Life (Basel). 2024 Jul 24;14(8):922. doi: 10.3390/life14080922.
Extrachromosomal circular DNA (eccDNA) is a form of a circular double-stranded DNA that exists independently of conventional chromosomes. eccDNA exhibits a broad and random distribution across eukaryotic cells and has been associated with tumor-related properties due to its ability to harbor the complete gene information of oncogenes. The complex and multifaceted mechanisms underlying eccDNA formation include pathways such as DNA damage repair, breakage-fusion-bridge (BFB) mechanisms, chromothripsis, and cell apoptosis. Of note, eccDNA plays a pivotal role in tumor development, genetic heterogeneity, and therapeutic resistance. The high copy number and transcriptional activity of oncogenes carried by eccDNA contribute to the accelerated growth of tumors. Notably, the amplification of oncogenes on eccDNA is implicated in the malignant progression of cancer cells. The improvement of high-throughput sequencing techniques has greatly enhanced our knowledge of eccDNA by allowing for a detailed examination of its genetic structures and functions. However, we still lack a comprehensive and efficient annotation for eccDNA, while challenges persist in the study and understanding of the functional role of eccDNA, emphasizing the need for the development of robust methodologies. The potential clinical applications of eccDNA, such as its role as a measurable biomarker or therapeutic target in diseases, particularly within the spectrum of human malignancies, is a promising field for future research. In conclusion, eccDNA represents a quite dynamic and multifunctional genetic entity with far-reaching implications in cancer pathogenesis and beyond. Further research is essential to unravel the molecular pathways of eccDNA formation, elucidate its functional roles, and explore its clinical applications. Addressing these aspects is crucial for advancing our understanding of genomic instability and developing novel strategies for tailored therapeutics, especially in cancer.
染色体外环状DNA（eccDNA）是一种环状双链DNA形式，独立于传统染色体存在。eccDNA在真核细胞中呈现广泛且随机的分布，由于其能够携带癌基因的完整基因信息，已与肿瘤相关特性相关联。eccDNA形成的复杂多面机制包括DNA损伤修复、断裂-融合-桥接（BFB）机制、染色体碎裂以及细胞凋亡等途径。值得注意的是，eccDNA在肿瘤发展、遗传异质性和治疗抗性中起关键作用。eccDNA携带的癌基因的高拷贝数和转录活性有助于肿瘤的加速生长。值得注意的是，eccDNA上癌基因的扩增与癌细胞的恶性进展有关。高通量测序技术的改进通过允许详细检查其遗传结构和功能，极大地增强了我们对eccDNA的认识。然而，我们仍然缺乏对eccDNA的全面有效注释，同时在eccDNA功能作用的研究和理解方面仍然存在挑战，这强调了开发强大方法的必要性。eccDNA的潜在临床应用，例如其作为疾病（特别是在人类恶性肿瘤范围内）中可测量的生物标志物或治疗靶点的作用，是未来研究的一个有前景的领域。总之，eccDNA代表了一个相当动态和多功能的遗传实体，在癌症发病机制及其他方面具有深远影响。进一步的研究对于揭示eccDNA形成的分子途径、阐明其功能作用以及探索其临床应用至关重要。解决这些方面对于推进我们对基因组不稳定性的理解以及开发定制治疗的新策略（尤其是在癌症方面）至关重要。
