Volume 65, Issue 2, Pages 274-277 (February 2014) Telomerase Reverse Transcriptase Gene Promoter Mutations Help Discern the Origin of Urogenital Tumors: A Genomic and Molecular Study  Song Wu, Peide Huang, Chong Li, Yi Huang, Xianxin Li, Yongqiang Wang, Chao Chen, Zhaojie Lv, Aifa Tang, Xiaojuan Sun, Jingxiao Lu, Weiping Li, Jie Zhou, Yaoting Gui, Fangjian Zhou, Daping Wang, Zhiming Cai  European Urology  Volume 65, Issue 2, Pages 274-277 (February 2014) DOI: 10.1016/j.eururo.2013.10.038 Copyright © 2013 European Association of Urology Terms and Conditions

Fig. 1 Functional analyses of telomerase reverse transcriptase (TERT) promoter mutations in transitional cell carcinoma cell lines and mutually exclusive analyses of TERT mutations with mutations in other bladder cancer genes. (a) −124 G>A or −146G>A mutation enhanced TERT expression. (b) The mutations generated de novo consensus binding motifs for v-ets avian erythroblastosis virus E26 oncogene homolog 1 (Ets1). The results of chromatin immunoprecipitation assays with antibodies against Ets1 showed a significant enrichment of the TERT promoter with the Ets1 antibodies in the mutant T24 cells but no enrichment in the WT T24 cells, compared with the nonspecific immunoglobulin G (IgG) control antibodies. (c) The mutations contributed to the migration of cancer cells. (d) Concurrent and mutually exclusive TERT mutations with mutations in other bladder cancer genes. For each gene (row) indicated, tumors (columns) with or without mutations are labeled in red or blue-green, respectively. (e) The chromosome instability (CIN) score of tumors with TERT mutation was significantly greater than tumors without TERT mutation. mRNA=messenger RNA; WT=wild type; TP53=tumor protein 53; RB1=retinoblastoma 1; FGFR3=fibroblast growth factor receptor 3; HRAS=Harvey rat sarcoma viral oncogene homolog; KRAS=Kirsten rat sarcoma viral oncogene homolog; UTX=lysine (K)-specific demethylase 6A (current Human Genome Organization [HUGO] symbol: KDM6A); MLL=lysine (K)-specific methyltransferase 2A (current HUGO symbol: KMT2A); MLL3=lysine (K)-specific methyltransferase 2C (current HUGO symbol: KMT2C); CREBBP=CREB binding protein; EP300=E1A binding protein p300; NCOR21=nuclear receptor corepressor 1; ARID1A=AT rich interactive domain 1A (SWI-like); CHD6=chromodomain helicase DNA binding protein 6. European Urology 2014 65, 274-277DOI: (10.1016/j.eururo.2013.10.038) Copyright © 2013 European Association of Urology Terms and Conditions

European Urology 2014 65, 274-277DOI: (10.1016/j.eururo.2013.10.038) Copyright © 2013 European Association of Urology Terms and Conditions