Telomerase regulation and telomere shortening act as a strong tumor suppressor mechanism in human somatic cells. Point mutations in the promoter of telomerase reverse transcriptase (TERT) are the most frequent non-coding mutation in cancer. These TERT promoter mutations (TPMs) create de novo ETS factor binding sites upstream of the start codon of the gene, which can be bound by different ETS factors. TPMs can occur early during tumorigenesis and are thought to be among the first mutations in melanoma, glioblastoma and hepatocellular carcinoma. Despite their association with increased TERT levels, TPMs do not prohibit telomere shortening and TPM-harboring cancers present with short telomeres. Their short telomere length combined with their high prevalence and specificity for cancer makes TPMs an attractive target for future therapeutic exploitation of telomerase inhibition and telomere deprotection-induced cell death.

中文翻译：

---

肿瘤发生过程中的TERT启动子突变和端粒。

端粒酶调节和端粒缩短是人类体细胞中强大的肿瘤抑制机制。端粒酶逆转录酶（TERT）启动子中的点突变是癌症中最常见的非编码突变。这些TERT启动子突变（TPM）在基因起始密码子上游创建了从头ETS因子结合位点，该位点可以被不同的ETS因子结合。TPM可以在肿瘤发生的早期发生，并且被认为是黑色素瘤，胶质母细胞瘤和肝细胞癌的首批突变之一。尽管它们与增加的TERT水平相关，但TPM并不能阻止端粒缩短和端粒短的癌症。