Heidenreich Barbara, Rachakonda P Sivaramakrishna, Hemminki Kari, Kumar Rajiv
Division of Molecular Genetic Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
Division of Molecular Genetic Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany; Center for Primary Health Care Research, Lund University, Malmö, Sweden.
Curr Opin Genet Dev. 2014 Feb;24:30-7. doi: 10.1016/j.gde.2013.11.005. Epub 2013 Dec 20.
Human telomerase reverse transcriptase (TERT) encodes a rate-limiting catalytic subunit of telomerase that maintains genomic integrity. TERT expression is mostly repressed in somatic cells with exception of proliferative cells in self-renewing tissues and cancer. Immortality associated with cancer cells has been attributed to telomerase over-expression. The precise mechanism behind the TERT activation in cancers has mostly remained unknown. The newly described germline and recurrent somatic mutations in melanoma and other cancers in the TERT promoter that create de novo E-twenty six/ternary complex factors (Ets/TCF) binding sites, provide an insight into the possible cause of tumor-specific increased TERT expression. In this review we discuss the discovery and possible implications of the TERT promoter mutations in melanoma and other cancers.
人端粒酶逆转录酶（TERT）编码端粒酶的一个限速催化亚基，该亚基维持基因组完整性。TERT表达在体细胞中大多受到抑制，但自我更新组织中的增殖细胞和癌细胞除外。癌细胞的永生性归因于端粒酶的过度表达。癌症中TERT激活背后的确切机制大多仍不清楚。新描述的黑色素瘤和其他癌症中TERT启动子的种系和复发性体细胞突变产生了新的E26/三元复合因子（Ets/TCF）结合位点，这为肿瘤特异性TERT表达增加的可能原因提供了线索。在本综述中，我们讨论了黑色素瘤和其他癌症中TERT启动子突变的发现及其可能的影响。
