文章：

癌症中的染色体外DNA

Extrachromosomal DNA in cancer

原文发布日期：2024-02-26

DOI: 10.1038/s41568-024-00669-8

类型: Review Article

开放获取: 否

英文摘要：

Extrachromosomal DNA (ecDNA) has recently been recognized as a major contributor to cancer pathogenesis that is identified in most cancer types and is associated with poor outcomes. When it was discovered over 60 years ago, ecDNA was considered to be rare, and its impact on tumour biology was not well understood. The application of modern imaging and computational techniques has yielded powerful new insights into the importance of ecDNA in cancer. The non-chromosomal inheritance of ecDNA during cell division results in high oncogene copy number, intra-tumoural genetic heterogeneity and rapid tumour evolution that contributes to treatment resistance and shorter patient survival. In addition, the circular architecture of ecDNA results in altered patterns of gene regulation that drive elevated oncogene expression, potentially enabling the remodelling of tumour genomes. The generation of clusters of ecDNAs, termed ecDNA hubs, results in interactions between enhancers and promoters in trans, yielding a new paradigm in oncogenic transcription. In this Review, we highlight the rapid advancements in ecDNA research, providing new insights into ecDNA biogenesis, maintenance and transcription and its role in promoting tumour heterogeneity. To conclude, we delve into a set of unanswered questions whose answers will pave the way for the development of ecDNA targeted therapeutic approaches.

摘要翻译： 

染色体外DNA（ecDNA）近年来被确认为癌症发病的主要因素，它存在于大多数癌症类型中，并与不良预后相关。60多年前刚发现时，ecDNA曾被认为很罕见，且其对肿瘤生物学的影响尚未被充分认知。现代成像与计算技术的应用为ecDNA在癌症中的重要性提供了强有力的新见解：ecDNA在细胞分裂过程中的非染色体遗传导致高癌基因拷贝数、肿瘤内遗传异质性和快速肿瘤进化，这些因素共同促成治疗耐药和患者生存期缩短。此外，ecDNA的环状结构改变了基因调控模式，驱动癌基因表达上调，可能促进肿瘤基因组重塑。ecDNA聚集形成的“ecDNA枢纽”能够实现增强子与启动子之间的反式相互作用，从而建立致癌转录的新范式。本文综述重点梳理ecDNA研究的快速进展，深入解析其生物发生、维持与转录机制，及其在促进肿瘤异质性中的作用。最后，我们探讨了一系列悬而未决的科学问题，这些问题的解答将为开发靶向ecDNA的治疗方法奠定基础。

原文链接：

Extrachromosomal DNA in cancer