端粒酶逆转录酶启动子的 DNA 甲基化及其对人类癌症的影响。
DNA methylation of the TERT promoter and its impact on human cancer.
机构信息
Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
出版信息
Curr Opin Genet Dev. 2020 Feb;60:17-24. doi: 10.1016/j.gde.2020.02.003. Epub 2020 Feb 27.
Telomere maintenance is a hallmark of human cancer that enables replicative immortality. Most cancer cells acquire telomere maintenance by telomerase activation through expression of telomerase reverse transcriptase (TERT), a rate-limiting component of the telomerase holoenzyme. Although multiple cancer-specific genetic alterations such as gain of TERT copy number and recurrent TERT promoter mutations (TPM) have been identified, the majority of cancers still express TERT via unknown mechanisms. In the last decade, DNA methylation of the TERT promoter emerged as a putative epigenetic regulatory mechanism of telomerase activation in cancer. Here, we comparatively discuss studies that investigated the DNA methylation landscape of the TERT promoter. We further review the biological and clinical impacts of TERT promoter hypermethylation in cancer and provide insight into future applications of this phenomenon.
端粒维持是人类癌症的一个标志，使细胞能够复制永生。大多数癌细胞通过端粒酶逆转录酶（TERT）的表达获得端粒维持，TERT 是端粒酶全酶的限速成分。尽管已经确定了多种癌症特异性遗传改变，如 TERT 拷贝数增加和 TERT 启动子突变（TPM）的反复出现，但大多数癌症仍通过未知机制表达 TERT。在过去的十年中，TERT 启动子的 DNA 甲基化已成为癌症中端粒酶激活的潜在表观遗传调控机制。在这里，我们比较性地讨论了研究 TERT 启动子 DNA 甲基化图谱的研究。我们进一步回顾了 TERT 启动子超甲基化在癌症中的生物学和临床影响，并深入探讨了这一现象的未来应用。
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