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.

中文翻译：

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TERT启动子的DNA甲基化及其对人类癌症的影响。

端粒的维持是人类癌症的特征，它使复制永生。大多数癌细胞通过端粒酶逆转录酶（TERT）的表达来激活端粒酶，端粒酶是端粒酶全酶的限速成分。尽管已经鉴定出多种癌症特异性遗传改变，例如获得TERT拷贝数和复发性TERT启动子突变（TPM），但大多数癌症仍通过未知机制表达TERT。在最近的十年中，TERT启动子的DNA甲基化已成为癌症中端粒酶激活的假定表观遗传调控机制。在这里，我们比较讨论研究TERT启动子的DNA甲基化态势的研究。