PURPOSE: The expression of the ETS-related gene (ERG) is low or undetectable in benign prostate epithelial cells. High prevalence of ERG overexpression in prostate cancer cells due to TMPRSS2-ERG fusions suggest for causal roles of ERG protein in the neoplastic process. TMPRSS2-ERG fusion junctions have been extensively studied in prostate cancer. However, virtually nothing is known about the nature of full-length transcripts and encoded proteins. This study focuses on qualitative and quantitative features of full-length TMPRSS2-ERG transcripts in prostate cancer. EXPERIMENTAL DESIGN: Full-length TMPRSS2-ERG transcripts were cloned and sequenced from a cDNA library generated from pooled RNA of six TMPRSS2-ERG fusion-positive prostate tumors. The encoded ERG proteins were analyzed in HEK293 cells. Copy numbers of TMPRSS2-ERG splice variants were determined by quantitative reverse transcription-PCR in laser capture microdissected prostate cancer cells. RESULTS: Two types of TMPRSS2-ERG cDNAs were identified: type I, which encodes full-length prototypical ERG protein (ERG1, ERG2, ERG3), and type II, encoding truncated ERG proteins lacking the ETS domain (ERG8 and a new variant, TEPC). In microdissected prostate tumor cells from 122 patients, relative abundance of these variants was in the following order: ERG8 > TEPC > ERG 3 > ERG1/2 with combined overexpression rate of 62.3% in prostate cancer. Increased ratio of type I over type II splice forms showed a trend of correlation with less favorable pathology and outcome. CONCLUSIONS: Qualitative and quantitative features of specific ERG splice variants defined here promise to enhance the utility of ERG as a biomarker and therapeutic target in prostate cancer.
PURPOSE: The expression of the ETS-related gene (ERG) is low or undetectable in benign prostate epithelial cells. High prevalence of ERG overexpression in prostate cancer cells due to TMPRSS2-ERG fusions suggest for causal roles of ERG protein in the neoplastic process. TMPRSS2-ERG fusion junctions have been extensively studied in prostate cancer. However, virtually nothing is known about the nature of full-length transcripts and encoded proteins. This study focuses on qualitative and quantitative features of full-length TMPRSS2-ERG transcripts in prostate cancer. EXPERIMENTAL DESIGN: Full-length TMPRSS2-ERG transcripts were cloned and sequenced from a cDNA library generated from pooled RNA of six TMPRSS2-ERG fusion-positive prostate tumors. The encoded ERG proteins were analyzed in HEK293 cells. Copy numbers of TMPRSS2-ERG splice variants were determined by quantitative reverse transcription-PCR in laser capture microdissected prostate cancer cells. RESULTS: Two types of TMPRSS2-ERG cDNAs were identified: type I, which encodes full-length prototypical ERG protein (ERG1, ERG2, ERG3), and type II, encoding truncated ERG proteins lacking the ETS domain (ERG8 and a new variant, TEPC). In microdissected prostate tumor cells from 122 patients, relative abundance of these variants was in the following order: ERG8 > TEPC > ERG 3 > ERG1/2 with combined overexpression rate of 62.3% in prostate cancer. Increased ratio of type I over type II splice forms showed a trend of correlation with less favorable pathology and outcome. CONCLUSIONS: Qualitative and quantitative features of specific ERG splice variants defined here promise to enhance the utility of ERG as a biomarker and therapeutic target in prostate cancer.
Authors: Ram-Shankar Mani; Matthew K Iyer; Qi Cao; J Chad Brenner; Lei Wang; Aparna Ghosh; Xuhong Cao; Robert J Lonigro; Scott A Tomlins; Sooryanarayana Varambally; Arul M Chinnaiyan Journal: Cancer Res Date: 2011-06-15 Impact factor: 12.701
Authors: Vladimir N Uversky; Vrushank Davé; Lilia M Iakoucheva; Prerna Malaney; Steven J Metallo; Ravi Ramesh Pathak; Andreas C Joerger Journal: Chem Rev Date: 2014-05-15 Impact factor: 60.622
Authors: Jennifer Cullen; Denise Young; Yongmei Chen; Michael Degon; James Farrell; Jason Sedarsky; Wagner Baptiste; Philip Rosen; Vladimir Tolstikov; Michael Kiebish; Jacob Kagan; Sudhir Srivastava; Huai-Ching Kuo; Joel T Moncur; Inger L Rosner; Niven Narain; Viatcheslav Akmaev; Gyorgy Petrovics; Albert Dobi; David G McLeod; Shiv Srivastava; Isabell A Sesterhenn Journal: Eur Urol Focus Date: 2017-03-11
Authors: Tao Liu; Mahmud Hossain; Athena A Schepmoes; Thomas L Fillmore; Lori J Sokoll; Scott R Kronewitter; Grant Izmirlian; Tujin Shi; Wei-Jun Qian; Robin J Leach; Ian M Thompson; Daniel W Chan; Richard D Smith; Jacob Kagan; Sudhir Srivastava; Karin D Rodland; David G Camp Journal: J Proteomics Date: 2012-02-13 Impact factor: 4.044