TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer.
Although common in hematologic and mesenchymal malignancies, recurrent gene fusions have not been well characterized in epithelial carcinomas. Recently, using a novel bioinformatic approach, we identified recurrent gene fusions between TMPRSS2 and the ETS family members ERG or ETV1 in the majority of prostate cancers. Here, we interrogated the expression of all ETS family members in prostate cancer profiling studies and identified marked overexpression of ETV4 in 2 of 98 cases. In one such case, we confirmed the overexpression of ETV4 using quantitative PCR, and by rapid amplification of cDNA ends, quantitative PCR, and fluorescence in situ hybridization, we show that the TMPRSS2 (21q22) and ETV4 (17q21) loci are fused in this case. This result defines a third molecular subtype of prostate cancer and supports the hypothesis that dysregulation of ETS family members through fusions with TMRPSS2 may be an initiating event in prostate cancer development.
Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109, USA.
Scott A
SA
Tomlins
Rohit
R
Mehra
Daniel R
DR
Rhodes
Lisa R
LR
Smith
Diane
D
Roulston
Beth E
BE
Helgeson
Xuhong
X
Cao
John T
JT
Wei
Mark A
MA
Rubin
Rajal B
RB
Shah
Arul M
AM
Chinnaiyan
D017500:Adenovirus E1A Proteins / Q000096:biosynthesis / Q000235:genetics*; D001483:Base Sequence; D020869:Gene Expression Profiling; D050939:Gene Fusion; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics*
D017500:Adenovirus E1A Proteins; C079853:ETV4 protein, human; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; C529662:TMPRSS2-ETV4 fusion protein, human; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human