The C228T mutation of TERT promoter frequently occurs in bladder cancer stem cells and contributes to tumorigenesis of bladder cancer.
The C228T mutation of TERT promoter frequently occurs in bladder cancer stem cells and contributes to tumorigenesis of bladder cancer.
复制标题
膀胱癌干细胞中TERT启动子C228T突变频繁发生并促进膀胱癌的发生
DOI：
10.18632/oncotarget.4295
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发表时间：
2015-08-14
期刊：
影响因子：
--
通讯作者：
Fan Z
中科院分区：
文献类型：
--
作者：
Li C;Wu S;Wang H;Bi X;Yang Z;Du Y;He L;Cai Z;Wang J;Fan Z
膀胱癌是世界范围内最常见的恶性肿瘤之一。膀胱癌干细胞（BCSC）最近已被分离，但尚未被定义。在这里，我们从膀胱肿瘤组织或正常膀胱干细胞（NBBC）从相邻的正常膀胱组织中分选BCSC。我们发现在BCSCs中存在TERT启动子的C228 T突变（chr5，1，295，228 C > T），而在NBBC中不存在。重要的是，在NBBC中引入C228T突变导致TERT过表达和膀胱癌的转化。在BCSC中将C228T突变恢复为T228C可以将TERT表达恢复到基础水平并消除肿瘤形成。此外，TERT启动子的C228T突变触发TERT表达，导致端粒酶活性增加。TERT表达水平与膀胱癌的临床严重程度和预后一致。
Bladder cancer is one of the most common malignant tumors worldwide. Bladder cancer stem cells (BCSCs) have been isolated recently but have not been defined yet. Here we sorted BCSCs from bladder tumor tissues or normal bladder stem cells (NBBCs) from adjacent normal bladder tissues. We found that the C228T mutation (chr5, 1, 295, 228 C > T) of TERT promoter frequently occurs in BCSCs, but not exist in NBBCs. Importantly, introducing the C228T mutation in NBBCs causes TERT overexpression and transformation of bladder cancer. Restoration of the C228T mutation to T228C in BCSCs can recover the TERT expression to a basal level and abolish tumor formation. Additionally, the C228T mutation of TERT promoter triggers TERT expression leading to increased telomerase activity. TERT expression levels are consistent with clinical severity and prognosis of bladder cancer.