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染色体外DNA在肿瘤发生和癌症治疗耐药性中的新见解

New insights of extrachromosomal DNA in tumorigenesis and therapeutic resistance of cancer.

作者信息

Qiu Hui, Shao Zhi-Ying, Wen Xin, Zhang Long-Zhen

机构信息

Cancer Institute, Xuzhou Medical University Xuzhou 221000, Jiangsu, China.

Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University Xuzhou 221000, Jiangsu, China.

出版信息

Am J Cancer Res. 2020 Dec 1;10(12):4056-4065. eCollection 2020.

Abstract

In the past few decades, the studies of extrachromosomal DNA (ecDNA), which existed independently of chromosomes, were tepid. However, recent studies on ecDNA rekindled the enthusiasm of oncologists for further studying ecDNA. In this review, we summarized the recent advances of ecDNA in oncogenesis and oncotherapy. ecDNA consists of highly open chromatin, and its circular structure enables ultra-long-range chromatin contacts. ecDNA is not inherited in accordance with Mendel's laws. Furthermore, ecDNA is widely existed in cancer cells, but almost never found in normal cells. It has been found that ecDNA played important roles in tumorigenesis and tumor progression, including oncogene amplification, tumor heterogeneity, enhancer hijacking and genomic rearrangement. More importantly, ecDNA is closely related to cancer treatment resistance. In hence, further understanding of ecDNA would contribute to developing innovative targeting ecDNA therapies.

摘要

在过去几十年里,对独立于染色体存在的染色体外DNA(ecDNA)的研究一直不温不火。然而,最近关于ecDNA的研究重新点燃了肿瘤学家进一步研究ecDNA的热情。在这篇综述中,我们总结了ecDNA在肿瘤发生和肿瘤治疗方面的最新进展。ecDNA由高度开放的染色质组成,其环状结构能够实现超远距离的染色质接触。ecDNA不按照孟德尔定律遗传。此外,ecDNA广泛存在于癌细胞中,但在正常细胞中几乎从未发现。已经发现ecDNA在肿瘤发生和肿瘤进展中发挥重要作用,包括癌基因扩增、肿瘤异质性、增强子劫持和基因组重排。更重要的是,ecDNA与癌症治疗耐药性密切相关。因此,进一步了解ecDNA将有助于开发创新的靶向ecDNA疗法。

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