Telomerase Reverse Transcriptase Gene Promoter Mutations Help Discern the Origin of Urogenital Tumors: A Genomic and Molecular Study
Telomerase Reverse Transcriptase Gene Promoter Mutations Help Discern the Origin of Urogenital Tumors: A Genomic and Molecular Study
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端粒酶逆转录酶基因启动子突变有助于辨别泌尿生殖肿瘤的起源：基因组和分子研究。
DOI：
10.1016/j.eururo.2013.10.038
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发表时间：
2014-02-01
期刊：
影响因子：
23.4
通讯作者：
Cai, Zhiming
中科院分区：
文献类型：
--
作者：
Wu, Song;Huang, Peide;Cai, Zhiming
端粒酶活性在几乎所有的肿瘤组织中都有表达，检测尿中端粒酶活性对膀胱癌的诊断和病情监测有重要意义。在这项研究中，我们筛选，桑格测序，302例患者的各种泌尿生殖系统癌症的端粒酶逆转录酶（TERT）基因的启动子的体细胞突变，并确定在泌尿生殖系统癌症的临床相关性的TERT启动子突变。还进行了体外测定以评价所发现的突变的功能影响。我们发现，在不同类型的泌尿生殖系统肿瘤（范围：0-63.7%）之间的TERT启动子的体细胞突变的频率变化很大，与尿路上皮癌显示最高的突变频率和前列腺癌显示没有突变。这些突变上调了TERT的表达，增强了肿瘤细胞的侵袭性。这些突变在患有侵袭性疾病和晚期肿瘤的老年患者中更普遍，并且与显著较短的生存时间相关。此外，我们还观察到一个显着的共同发生的突变之间的TERT启动子和肿瘤蛋白51/视网膜母细胞瘤1（TP 53/RB 1）信号通路。因此，TERT启动子突变可能作为泌尿生殖系统肿瘤的鉴别诊断和监测的重要标志物。(C)2013年欧洲泌尿外科协会。由Elsevier B出版。V.保留所有权利。
Activation of telomerase can be observed in almost all human tumor histotypes and detection of the urinary telomerase activities is useful for the diagnosis and surveillance of bladder cancer. In this study, we screened, by Sanger sequencing, 302 patients with various urogenital cancers for somatic mutations in the promoter of the telomerase reverse transcriptase (TERT) gene and determined the clinical relevance of TERT promoter mutations in urogenital cancer. In vitro assays were also performed to evaluate the functional influence of the discovered mutations. We found that the frequencies of somatic mutations in the TERT promoter varied substantially between different types of urogenital tumors (range: 0-63.7%), with urothelial carcinomas showing the highest mutation frequency and prostate cancer showing no mutation. The mutations upregulated the expression of TERT and enhanced the invasiveness of the tumor cells. The mutations were more prevalent in older patients with invasive diseases and advanced tumor stages, and were associated with significantly shorter survival time. Moreover, we also observed a significant co-occurrence of mutations between the TERT promoter and the tumor protein 51/retinoblastoma1 (TP53/RB1) signaling pathway. Hence, TERT promoter mutations may serve as important markers for the differential diagnosis and surveillance of urogenital tumors. (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved.