Cheng Liang, Zhang Shaobo, Wang Mingsheng, Lopez-Beltran Antonio
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA; Department of Pathology and Laboratory Medicine, Warren Alpert Medical School of Brown University and Lifespan Academic Medical Center, Providence, RI, 02903, USA.
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Hum Pathol. 2023 Mar;133:56-75. doi: 10.1016/j.humpath.2022.06.005. Epub 2022 Jun 11.
The telomerase reverse transcriptase (TERT) promoter mutations are associated with increased TERT mRNA and TERT protein levels, telomerase activity, and shorter but stable telomere length. TERT promoter mutation is the most common mutation that occurs in approximately 60-80% of patients with bladder cancer. The TERT promoter mutations occur in a wide spectrum of urothelial lesions, including benign urothelial proliferation and tumor-like conditions, benign urothelial tumors, premalignant and putative precursor lesions, urothelial carcinoma and its variants, and nonurothelial malignancies. The prevalence and incidence of TERT promoter mutations in a total of 7259 cases from the urinary tract were systematically reviewed. Different platforms of TERT promoter mutation detection were presented. In this review, we also discussed the significance and clinical implications of TERT promoter mutation detection in urothelial tumorigenesis, surveillance and early detection, diagnosis, differential diagnosis, prognosis, prediction of treatment responses, and clinical outcome. Identification of TERT promoter mutations from urine or plasma cell-free DNA (liquid biopsy) will facilitate bladder cancer screening program and optimal clinical management. A better understanding of TERT promoter mutation and its pathway would open new therapeutic avenues for patients with bladder cancer.
端粒酶逆转录酶（TERT）启动子突变与TERT信使核糖核酸（mRNA）及TERT蛋白水平升高、端粒酶活性以及较短但稳定的端粒长度相关。TERT启动子突变是最常见的突变，约60% - 80%的膀胱癌患者会出现这种突变。TERT启动子突变发生于广泛的尿路上皮病变中，包括良性尿路上皮增生和肿瘤样病变、良性尿路上皮肿瘤、癌前和假定的前驱病变、尿路上皮癌及其变体，以及非尿路上皮恶性肿瘤。对总共7259例尿路病例中TERT启动子突变的患病率和发病率进行了系统综述。介绍了TERT启动子突变检测的不同平台。在本综述中，我们还讨论了TERT启动子突变检测在尿路上皮肿瘤发生、监测与早期检测、诊断、鉴别诊断、预后、治疗反应预测及临床结局中的意义和临床应用。从尿液或血浆游离DNA（液体活检）中鉴定TERT启动子突变将有助于膀胱癌筛查计划和优化临床管理。更好地理解TERT启动子突变及其途径将为膀胱癌患者开辟新的治疗途径。
