超越染色体:解码人类恶性肿瘤中染色体外环状 DNA (eccDNA) 重要性的最新进展

Life Pub Date : 2024-07-24 DOI:10.3390/life14080922
P. Tsiakanikas, Konstantina Athanasopoulou, Ioanna A. Darioti, Vasiliki Taxiarchoula Agiassoti, Stamatis Theocharis, Andreas Scorilas, P. Adamopoulos
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引用次数: 0

摘要

染色体外环状脱氧核糖核酸(ccDNA)是一种独立于传统染色体的环状双链脱氧核糖核酸。ccDNA在真核细胞中呈现出广泛而随机的分布,并因其能够携带完整的癌基因信息而与肿瘤相关。eccDNA形成的机制复杂多样,包括DNA损伤修复、断裂-融合桥(BFB)机制、染色体分裂和细胞凋亡等途径。值得注意的是,ccDNA 在肿瘤发生、遗传异质性和耐药性方面起着关键作用。ccDNA携带的癌基因的高拷贝数和转录活性导致肿瘤加速生长。值得注意的是,ccDNA 上的癌基因扩增与癌细胞的恶性发展有关。高通量测序技术的改进大大提高了我们对ccDNA的认识,使我们能够详细研究其遗传结构和功能。然而,我们仍然缺乏对cccDNA全面而有效的注释,同时在研究和了解cccDNA的功能作用方面仍然存在挑战,这就强调了开发可靠方法的必要性。eccDNA的潜在临床应用,如在疾病(尤其是人类恶性肿瘤)中作为可测量的生物标志物或治疗靶点,是未来很有希望的研究领域。总之,ccDNA 是一个相当活跃的多功能基因实体,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。解决这些方面的问题,对于加深我们对基因组不稳定性的理解和开发新的定制治疗策略至关重要,尤其是在癌症领域。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Beyond the Chromosome: Recent Developments in Decoding the Significance of Extrachromosomal Circular DNA (eccDNA) in Human Malignancies
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.
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