Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer.
Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. We used a bioinformatics approach to discover candidate oncogenic chromosomal aberrations on the basis of outlier gene expression. Two ETS transcription factors, ERG and ETV1, were identified as outliers in prostate cancer. We identified recurrent gene fusions of the 5' untranslated region of TMPRSS2 to ERG or ETV1 in prostate cancer tissues with outlier expression. By using fluorescence in situ hybridization, we demonstrated that 23 of 29 prostate cancer samples harbor rearrangements in ERG or ETV1. Cell line experiments suggest that the androgen-responsive promoter elements of TMPRSS2 mediate the overexpression of ETS family members in prostate cancer. These results have implications in the development of carcinomas and the molecular diagnosis and treatment of prostate cancer.
Tomlins
Scott A
SA
Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109-0602, USA.
Rhodes
Daniel R
DR
Perner
Sven
S
Dhanasekaran
Saravana M
SM
Mehra
Rohit
R
Sun
Xiao-Wei
XW
Varambally
Sooryanarayana
S
Cao
Xuhong
X
Tchinda
Joelle
J
Kuefer
Rainer
R
Lee
Charles
C
Montie
James E
JE
Shah
Rajal B
RB
Pienta
Kenneth J
KJ
Rubin
Mark A
MA
Chinnaiyan
Arul M
AM
D000728:Androgens / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000071230:Transcriptional Regulator ERG; D014178:Translocation, Genetic
D000728:Androgens; D004268:DNA-Binding Proteins; C072312:ERG protein, human; C095239:ETV1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C409042:TMPRSS3 protein, human