结直肠癌中的圆形外染色体DNA:发生、功能和作为治疗靶点的潜力。
Extrachromosomal circular DNA in colorectal cancer: biogenesis, function and potential as therapeutic target.
发表日期:2023 Mar 01
作者:
Yinnan Chen, Quanpeng Qiu, Junjun She, Jun Yu
来源:
ONCOGENE
摘要:
超染色体环形DNA(ecDNA)自其发现半个多世纪以来重新引起了人们的关注,成为肿瘤进化的重要推动因素。 ecDNA在许多类型的癌症中高度普遍,包括结直肠癌(CRC),这是全球最致命的癌症之一。 ecDNA在CRC中独立于典型染色体改变的调节癌基因表达,肿瘤内异质性和治疗耐药性方面发挥着至关重要的作用。此外,ecDNA的存在与患者的预后有关,因为基于ecDNA的癌基因扩增会对临床结果产生不利影响。最近对ecDNA的理解给CRC的发病机制增加了额外的复杂性。在本综述中,我们将讨论在CRC中ecDNA产生机制和独特特征的当前认识。此外,我们将研究ecDNA如何介导癌基因过度表达,基因调控和与主动染色质的拓扑相互作用,从而促进遗传异质性,加速CRC恶性化并增加快速适应治疗耐药性。最后,我们将讨论ecDNA在CRC中的潜在诊断和治疗意义。 ©2023作者(们)。
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.© 2023. The Author(s).