Department of Urology, University of Ulm, Ulm, Germany.
Department of Biology, Jack Birch Unit of Molecular Carcinogenesis, University of York, York, UK.
Nat Rev Urol. 2018 Jun;15(6):386-393. doi: 10.1038/s41585-018-0001-5.
Telomerase activity imparts eukaryotic cells with unlimited proliferation capacity, one of the cancer hallmarks. Over 90% of human urothelial carcinoma of the bladder (UCB) tumours are positive for telomerase activity. Telomerase activation can occur through several mechanisms. Mutations in the core promoter region of the human telomerase reverse transcriptase gene (TERT) cause telomerase reactivation in 60-80% of UCBs, whereas the prevalence of these mutations is lower in urothelial cancers of other origins. TERT promoter mutations are the most frequent genetic alteration across all stages of UCB, indicating a strong selection pressure during neoplastic transformation. TERT promoter mutations could arise during regeneration of normal urothelium and, owing to consequential telomerase reactivation, might be the basis of UCB initiation, which represents a new model of urothelial cancer origination. In the future, TERT promoter mutations and telomerase activity might have diagnostic and therapeutic applications in UCB.
端粒酶活性赋予真核细胞无限的增殖能力，这是癌症的标志之一。超过 90%的人膀胱癌（UCB）肿瘤中端粒酶活性呈阳性。端粒酶的激活可以通过几种机制发生。人端粒酶逆转录酶基因（TERT）核心启动子区域的突变导致 60-80%的 UCB 中端粒酶重新激活，而在其他来源的尿路上皮癌中，这些突变的发生率较低。TERT 启动子突变是 UCB 所有阶段最常见的遗传改变，表明在肿瘤转化过程中存在强烈的选择压力。TERT 启动子突变可能发生在正常尿路上皮再生过程中，由于随后的端粒酶重新激活，可能是 UCB 起始的基础，这代表了一种新的尿路上皮癌起源模型。在未来，TERT 启动子突变和端粒酶活性可能在 UCB 的诊断和治疗中有应用。
