PMID- 20118910 OWN - NLM STAT- MEDLINE DCOM- 20100615 LR - 20230210 IS - 1530-0285 (Electronic) IS - 0893-3952 (Print) IS - 0893-3952 (Linking) VI - 23 IP - 4 DP - 2010 Apr TI - Prevalence of TMPRSS2-ERG and SLC45A3-ERG gene fusions in a large prostatectomy cohort. PG - 539-46 LID - 10.1038/modpathol.2009.193 [doi] AB - The majority of prostate cancers harbor recurrent gene fusions between the hormone-regulated TMPRSS2 and members of the ETS family of transcription factors, most commonly ERG. Prostate cancer with ERG rearrangements represent a distinct sub-class of tumor based on studies reporting associations with histomorphologic features, characteristic somatic copy number alterations, and gene expression signatures. This study describes the frequency of ERG rearrangement prostate cancer and three 5 prime (5') gene fusion partners (ie, TMPRSS2, SLC45A3, and NDRG1) in a large prostatectomy cohort. ERG gene rearrangements and mechanism of rearrangement, as well as rearrangements of TMPRSS2, SLC45A3, and NDRG1, were assessed using fluorescence in situ hybridization (FISH) on prostate cancer samples from 614 patients treated using radical prostatectomy. ERG rearrangement occurred in 53% of the 540 assessable cases. TMPRSS2 and SLC45A3 were the only 5' partner in 78% and 6% of these ERG rearranged cases, respectively. Interestingly, 11% of the ERG rearranged cases showed concurrent TMPRSS2 and SLC45A3 rearrangements. TMPRSS2 or SLC45A3 rearrangements could not be identified for 5% of the ERG rearranged cases. From these remaining cases we identified one case with NDRG1 rearrangement. We did not observe any associations with pathologic parameters or clinical outcome. This is the first study to describe the frequency of SLC45A3-ERG fusions in a large clinical cohort. Most studies have assumed that all ERG rearranged prostate cancers harbor TMPRSS2-ERG fusions. This is also the first study to report concurrent TMPRSS2 and SLC45A3 rearrangements in the same tumor focus, suggesting additional complexity that had not been previously appreciated. This study has important clinical implications for the development of diagnostic assays to detect ETS rearranged prostate cancer. Incorporation of these less common ERG rearranged prostate cancer fusion assays could further increase the sensitivity of the current PCR-based approaches. FAU - Esgueva, Raquel AU - Esgueva R AD - Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA. FAU - Perner, Sven AU - Perner S FAU - J LaFargue, Christopher AU - J LaFargue C FAU - Scheble, Veit AU - Scheble V FAU - Stephan, Carsten AU - Stephan C FAU - Lein, Michael AU - Lein M FAU - Fritzsche, Florian R AU - Fritzsche FR FAU - Dietel, Manfred AU - Dietel M FAU - Kristiansen, Glen AU - Kristiansen G FAU - Rubin, Mark A AU - Rubin MA LA - eng GR - R01 CA125612/CA/NCI NIH HHS/United States GR - R01 CA125612-03/CA/NCI NIH HHS/United States GR - CA125612/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100129 PL - United States TA - Mod Pathol JT - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JID - 8806605 RN - 0 (ERG protein, human) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (TMPRSS2-ERG fusion protein, human) RN - 0 (Trans-Activators) RN - 0 (Transcriptional Regulator ERG) SB - IM MH - Adult MH - Aged MH - Cohort Studies MH - Gene Rearrangement MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Oncogene Proteins, Fusion/*genetics MH - Prevalence MH - Prostatectomy MH - Prostatic Neoplasms/*genetics/surgery MH - Tissue Array Analysis MH - Trans-Activators/*genetics MH - Transcriptional Regulator ERG PMC - PMC2848699 MID - NIHMS165730 EDAT- 2010/02/02 06:00 MHDA- 2010/06/16 06:00 PMCR- 2010/10/01 CRDT- 2010/02/02 06:00 PHST- 2010/02/02 06:00 [entrez] PHST- 2010/02/02 06:00 [pubmed] PHST- 2010/06/16 06:00 [medline] PHST- 2010/10/01 00:00 [pmc-release] AID - S0893-3952(22)02733-8 [pii] AID - 10.1038/modpathol.2009.193 [doi] PST - ppublish SO - Mod Pathol. 2010 Apr;23(4):539-46. doi: 10.1038/modpathol.2009.193. Epub 2010 Jan 29.