title: Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 gene fusions in prostate cancer.
abstract: 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.
authors.affiliation: Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0602, USA.
authors.forename: Beth E
authors.initials: BE
authors.lastname: Helgeson
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.forename: Nameeta
authors.initials: N
authors.lastname: Shah
authors.forename: Bharathi
authors.initials: B
authors.lastname: Laxman
authors.forename: Qi
authors.initials: Q
authors.lastname: Cao
authors.forename: John R
authors.initials: JR
authors.lastname: Prensner
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cao
authors.forename: Nirmish
authors.initials: N
authors.lastname: Singla
authors.forename: James E
authors.initials: JE
authors.lastname: Montie
authors.forename: Sooryanarayana
authors.initials: S
authors.lastname: Varambally
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
mesh_terms: D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D050596:Oncogene Fusion; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D015514:Oncogene Proteins, Fusion; C526547:Slc45A3-ETV5 fusion protein, human; C526546:TMPRSS2-ETV5 fusion protein, human