Originating but free from chromosomal DNA, extrachromosomal circular DNAs (eccDNAs) are organized in circular form and have long been found in unicellular and multicellular eukaryotes. Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA, for which few detection methods are available. Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation, evolution, and drug resistance as well as aging, genomic diversity, and other biological processes, bringing it back to the research hotspot. Several mechanisms of eccDNA formation have been proposed, including the breakage-fusion-bridge (BFB) and translocation-deletion-amplification models. Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health. The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites. The present review summarized the research history, biogenesis, and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction. We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection, prognosis, and treatment of gynecologic tumors. This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.

中文翻译：

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对妇科肿瘤和生殖中染色体外环状 DNA 的创新见解。

起源于但不含染色体 DNA 的染色体外环状 DNA (eccDNA) 以环状形式组织，长期以来一直在单细胞和多细胞真核生物中发现。它们的生物发生和功能知之甚少，因为它们的特征是与线性 DNA 具有序列同源性，对此几乎没有可用的检测方法。近年来高通量测序技术的进展揭示了eccDNA在肿瘤形成、进化、耐药以及衰老、基因组多样性等生物过程中发挥着重要作用，使其重新成为研究热点。已经提出了 eccDNA 形成的几种机制，包括断裂-融合-桥 (BFB) 和易位-缺失-扩增模型。妇科肿瘤和胚胎及胎儿发育障碍是人类生殖健康的主要威胁。自从首次在猪精子中发现 eccDNA 和在卵巢癌腹水中发现双分钟以来，eccDNA 在这些病理过程中的作用已得到部分阐明。本文综述了 eccDNA 的研究历史、生物起源和目前可用的检测和分析方法，并阐明了它们在妇科肿瘤和生殖中的作用。我们还提出将eccDNAs作为药物靶点和液体活检标志物用于妇科肿瘤的产前诊断和早期检测、预后判断和治疗。该综述为未来研究 eccDNA 在重要生理和病理过程中的复杂调控网络奠定了理论基础。