The C228T mutation of TERT promoter frequently occurs in bladder cancer stem cells and contributes to tumorigenesis of bladder cancer
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Chong Li1,2,*, Song Wu2,*, Haifeng Wang3,*, Xingang Bi4,*, Zhao Yang1,*, Ying Du1, Luyun He1, Zhiming Cai2, Jiansong Wang3, Zusen Fan1
1CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
2Department of Urology, The Second People’s Hospital of Shenzhen, Shenzhen 518035, China
3Department of Urology, The Second Affiliated Hospital of Kunming Medical College, Kunming 650101, China
4Cancer Institute & Hospital Chinese Academy of Medical Sciences, Beijing 100021, China
*These authors have contributed equally to this work
Zusen Fan, e-mail: [email protected]
Zhiming Cai, e-mail: [email protected]
Jiansong Wang, e-mail: [email protected]
Keywords: bladder cancer stem cells, C228T mutation, telomerase reverse transcriptase (TERT), tumorigenesis
Received: April 10, 2015 Accepted: June 04, 2015 Published: June 17, 2015
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.
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