The TERT promoter and FGFR3 gene mutations are two of the most common genetic events in urothelial bladder cancer (UBC), and these mutation assays in patient urine have been shown to be promising biomarkers for UBC diagnosis and surveillance. These results were obtained mainly from studies of patients with UBC in Western countries, and little is known about such information in Han Chinese patients with UBC. In the present study, we addressed this issue by analyzing tumors from 182 Han Chinese patients with UBC and urine samples from 102 patients for mutations in the TERT promoter and FGFR3 and TERT mRNA expression in tumors and/or urine. TERT promoter and FGFR3 mutations were identified in 87 of 182 (47.8%) and 7 of 102 (6.7%) UBC cases, respectively. In 46 urine samples from patients with TERT promoter mutation-carrying tumors, the mutant promoter was detected in 24 (52%) prior to operation and disappeared in most examined urine samples (80%) taken 1 week after operation. TERT mRNA was detected in urine derived from 46 of 49 patients (94%) that was analyzed before operation independently of the presence of TERT promoter mutations. Collectively, FGFR3 mutations occur at a very low rate in Han Chinese UBC and cannot serve as diagnostic markers for Chinese patients. Han Chinese patients with UBC have relatively low TERT promoter mutation frequency compared with patients in Western countries, and simultaneous detection of both mutant TERT promoter and TERT mRNA improves sensitivity and specificity of urine-based diagnosis.
摘要
TERT 启动子和 FGFR3 基因突变是膀胱尿路上皮癌 (UBC) 中两个最常见的遗传事件，并且已经显示患者尿中的这些突变分析是用于 UBC 诊断和监测的有前景的生物标志物。这些结果主要从西方国家 UBC 患者的研究中获得，但关于中国汉族 UBC 患者的这类信息知之甚少。在本研究中，通过对源于 182 位中国汉族 UBC 患者的肿瘤和源于 102 位患者的尿样分析 TERT 启动子和 FGFR3 中的突变以及肿瘤和/或尿中的 TERT mRNA 表达，我们解决了这个问题。分别在 87/182 (47.8%) 的 UBC 病例和 7/102 (6.7%) 的 UBC 病例中鉴定出 TERT 启动子和 FGFR3 突变。在源自 TERT 启动子突变携带型肿瘤患者的 46 份尿样中，手术前的 24 (52%) 份尿样中检出突变启动子并且该启动子在手术后 1 周取得的大部分所查尿样 (80%) 中消失。在 46/49 (94%) 位患者于手术前分析的尿中检出 TERT mRNA，这与 TERT 启动子突变的存在无关。总体而言，FGFR3 突变以很低比率出现在中国汉族 UBC 患者中且不能充当中国患者的诊断标志物。与西方国家的患者相比，中国汉族 UBC 患者具有相对低的 TERT 启动子突变频率，并且同时检测突变 TERT 启动子和 TERT mRNA 改善了基于尿液诊断的灵敏性和特异性。The Oncologist 2015; 20:263–269
Keywords: FGFR3; TERT; Telomerase; Urinary markers; Urothelial bladder cancer.
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