Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of High Talent, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Oncogene. 2023 Mar;42(13):941-951. doi: 10.1038/s41388-023-02640-7. Epub 2023 Mar 1.
Extrachromosomal circular DNA (ecDNA) has gained renewed interest since its discovery more than half a century ago, emerging as critical driver of tumor evolution. ecDNA is highly prevalent in many types of cancers, including colorectal cancer (CRC), which is one of the most deadly cancers worldwide. ecDNAs play an essential role in regulating oncogene expression, intratumor heterogeneity, and resistance to therapy independently of canonical chromosomal alterations in CRC. Furthermore, the existence of ecDNAs is attributed to the patient's prognosis, since ecDNA-based oncogene amplification adversely affects clinical outcomes. Recent understanding of ecDNA put an extra layer of complexity in the pathogenesis of CRC. In this review, we will discuss the current understanding on mechanisms of biogenesis, and distinctive features of ecDNA in CRC. In addition, we will examine how ecDNAs mediate oncogene overexpression, gene regulation, and topological interactions with active chromatin, which facilitates genetic heterogeneity, accelerates CRC malignancy, and enhances rapid adaptation to therapy resistance. Finally, we will discuss the potential diagnostic and therapeutic implications of ecDNAs in CRC.
染色体外环状 DNA（ecDNA）在半个多世纪前被发现以来，重新引起了人们的兴趣，它已成为肿瘤进化的关键驱动因素。ecDNA 在许多类型的癌症中都很普遍，包括结直肠癌（CRC），这是全球最致命的癌症之一。ecDNAs 在调节致癌基因表达、肿瘤内异质性和对治疗的耐药性方面发挥着重要作用，而不依赖于 CRC 中典型的染色体改变。此外，ecDNA 的存在归因于患者的预后，因为基于 ecDNA 的致癌基因扩增会对临床结果产生不利影响。最近对 ecDNA 的认识为 CRC 的发病机制增加了一层复杂性。在这篇综述中，我们将讨论 ecDNA 在 CRC 中的生物发生机制和独特特征的最新理解。此外，我们还将研究 ecDNA 如何介导致癌基因过表达、基因调控以及与活性染色质的拓扑相互作用，这些作用促进了遗传异质性、加速了结直肠癌的恶性转化，并增强了对治疗耐药性的快速适应。最后，我们将讨论 ecDNA 在 CRC 中的潜在诊断和治疗意义。
