TY - JOUR
T1 - Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 gene fusions in prostate cancer
AU - Helgeson, Beth E.
AU - Tomlins, Scott A.
AU - Shah, Nameeta
AU - Laxman, Bharathi
AU - Cao, Qi
AU - Prensner, John R.
AU - Cao, Xuhong
AU - Singla, Nirmish
AU - Montie, James E.
AU - Varambally, Sooryanarayana
AU - Mehra, Rohit
AU - Chinnaiyan, Arul M.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/1/1
Y1 - 2008/1/1
N2 - Recurrent gene fusions involving oncogenic ETS transcription factors (including ERG, ETV1, and ETV4) have been identified in a large fraction of prostate cancers. The most common fusions contain the 5′ untranslated region of TMPRSS2 fused to ERG. Recently, we identified additional 5′ partners in ETV1 fusions, including TMPRSS2, SLC45A3, HERV-K_22q11.23, C15ORF21, and HNRPA2B1. Here, we identify ETV5 as the fourth ETS family member involved in recurrent gene rearrangements in prostate cancer. Characterization of two cases with ETV5 outlier expression by RNA ligase-mediated rapid amplification of cDNA ends identified one case with a TMPRSS2:ETV5 fusion and one case with a SLC45A3:ETV5 fusion. We confirmed the presence of these fusions by quantitative PCR and fluorescence in situ hybridization. In vitro recapitulation of ETV5 overexpression induced invasion in RWPE cells, a benign immortalized prostatic epithelial cell line. Expression profiling and an integrative molecular concepts analysis of RWPE-ETV5 cells also revealed the induction of an invasive transcriptional program, consistent with ERG and ETV1 overexpression in RWPE cells, emphasizing the functional redundancy of ETS rearrangements. Together, our results suggest that the family of 5′ partners previously identified in ETV1 gene fusions can fuse with other ETS family members, suggesting numerous rare gene fusion permutations in prostate cancer.
AB - Recurrent gene fusions involving oncogenic ETS transcription factors (including ERG, ETV1, and ETV4) have been identified in a large fraction of prostate cancers. The most common fusions contain the 5′ untranslated region of TMPRSS2 fused to ERG. Recently, we identified additional 5′ partners in ETV1 fusions, including TMPRSS2, SLC45A3, HERV-K_22q11.23, C15ORF21, and HNRPA2B1. Here, we identify ETV5 as the fourth ETS family member involved in recurrent gene rearrangements in prostate cancer. Characterization of two cases with ETV5 outlier expression by RNA ligase-mediated rapid amplification of cDNA ends identified one case with a TMPRSS2:ETV5 fusion and one case with a SLC45A3:ETV5 fusion. We confirmed the presence of these fusions by quantitative PCR and fluorescence in situ hybridization. In vitro recapitulation of ETV5 overexpression induced invasion in RWPE cells, a benign immortalized prostatic epithelial cell line. Expression profiling and an integrative molecular concepts analysis of RWPE-ETV5 cells also revealed the induction of an invasive transcriptional program, consistent with ERG and ETV1 overexpression in RWPE cells, emphasizing the functional redundancy of ETS rearrangements. Together, our results suggest that the family of 5′ partners previously identified in ETV1 gene fusions can fuse with other ETS family members, suggesting numerous rare gene fusion permutations in prostate cancer.
UR - http://www.scopus.com/inward/record.url?scp=39049170313&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=39049170313&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-5352
DO - 10.1158/0008-5472.CAN-07-5352
M3 - Article
C2 - 18172298
AN - SCOPUS:39049170313
SN - 0008-5472
VL - 68
SP - 73
EP - 80
JO - Cancer research
JF - Cancer research
IS - 1
ER -