SLC45A3 Is a Common ETS Family Fusion Partner in Prostate Cancer
S Perner, D Pflueger, DS Rickman, CJ LaFargue, MA Svensson, F Demichelis, C Stephan, M Dietel, FR Fritzsche, B Han, N Palanisamy, R Mehra, Y Allory, P Maille, A de la Taille, R Kuefer, AK Tewari, AM Chinnaiyan, G Kristiansen, MA Rubin. Weill Cornell Medical Center, New York, NY; Charit-University Hospital of Berlin, Berlin, Germany; University Hospital of Zurich, Zurich, Switzerland; University of Michigan, Ann Arbor, MI; CHU Mondor, Crteil, France; University Hospital Ulm, Ulm, Germany; Weill Cornell Medical College, New York, NY
Background: Recurrent gene fusions between TMPRSS2 and the ETS family transcription factors, most commonly ERG, have been identified in the majority of prostate cancers (PCa). The objective of this study was to characterize a novel gene fusion involving ERG.
Design: ERG and SLC45A3 gene rearrangements were assessed on 634 PCa samples using fluorescence in-situ hybridization (FISH). Gene fusion transcripts and ERG mRNA levels were characterized in 101 PCa samples using conventional and quantitative real-time reverse transcription-PCR.
Results: At the genomic and transcript level, we identified a novel gene fusion between the promoter of SLC45A3 and ERG. This fusion yielded ERG mRNA over-expression with levels comparable to those observed in samples harboring the TMPRSS2-ERG fusion. 553 samples could be assessed for ERG and SLC45A3 rearrangement. 37 samples (7%) showed ERG and SLC45A3 rearrangement, most likely resulting in a SLC45A3-ERG fusion, 17 samples (3%) showed SLC45A3 rearrangment only, and 267 samples (48%) showed ERG rearrangement only. Consistent with other studies, we found 55% samples with ERG rearrangement. To date, this is the largest PCa cohort assessed for ERG rearrangement. We found high levels of ERG mRNA overexpression in 90% (26/29) samples that demonstrated ERG rearrangement. We detected 7 TMPRSS2-ERG isoforms but did not observe a relationship between isoform expression and level of ERG over-expression.
Conclusions: Based on the characterization of 634 prostate cancer samples, we found that SLC45A3, a prostate-specific, androgen-regulated gene, represents the second most common 5' fusion partner of ETS genes in prostate cancer. Given the association between ERG gene rearrangement and prostate cancer progression, we hypothesize that tumors harboring the SLC45A3-ERG fusion may demonstrate the same clinical course.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 11:00 AM
Platform Session: Section A, Monday Morning