title: Delineation of TMPRSS2-ERG splice variants in prostate cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.affiliation: Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Rockville, Maryland 20852, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Albert
authors.initials: A
authors.lastname: Dobi
authors.forename: Taduru
authors.initials: T
authors.lastname: Sreenath
authors.forename: Christopher
authors.initials: C
authors.lastname: Cook
authors.forename: Atekelt Y
authors.initials: AY
authors.lastname: Tadase
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Ravindranath
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cullen
authors.forename: Bungo
authors.initials: B
authors.lastname: Furusato
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Chen
authors.forename: Rajesh L
authors.initials: RL
authors.lastname: Thangapazham
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mohamed
authors.forename: Chen
authors.initials: C
authors.lastname: Sun
authors.forename: Isabell A
authors.initials: IA
authors.lastname: Sesterhenn
authors.forename: David G
authors.initials: DG
authors.lastname: McLeod
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Petrovics
authors.forename: Shiv
authors.initials: S
authors.lastname: Srivastava
mesh_terms: D017398:Alternative Splicing; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
chemical_list: D014408:Biomarkers, Tumor; D018076:DNA, Complementary; C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human