title: The C228T mutation of TERT promoter frequently occurs in bladder cancer stem cells and contributes to tumorigenesis of bladder cancer.
abstract: 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.
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|Department of Urology, The Second People's Hospital of Shenzhen, Shenzhen 518035, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Urology, The Second People's Hospital of Shenzhen, Shenzhen 518035, China.
authors.forename: Song
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Kunming Medical College, Kunming 650101, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Cancer Institute & Hospital Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Bi
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Du
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Luyun
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Urology, The Second People's Hospital of Shenzhen, Shenzhen 518035, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Kunming Medical College, Kunming 650101, China.
authors.forename: Jiansong
authors.initials: J
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zusen
authors.initials: Z
authors.lastname: Fan
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000201:enzymology*; D010641:Phenotype; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics*; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C509186:TERT protein, human; D019098:Telomerase
keywords: C228T mutation; bladder cancer stem cells; telomerase reverse transcriptase (TERT); tumorigenesis