PMID- 23352841 OWN - NLM STAT- MEDLINE DCOM- 20130412 LR - 20211021 IS - 2210-7762 (Print) VI - 206 IP - 1-2 DP - 2013 Jan-Feb TI - A novel four-color fluorescence in situ hybridization assay for the detection of TMPRSS2 and ERG rearrangements in prostate cancer. PG - 1-11 LID - S2210-7762(12)00279-7 [pii] LID - 10.1016/j.cancergen.2012.12.004 [doi] AB - Since the identification of the TMPRSS2-ERG rearrangement as the most common fusion event in prostate cancer, various methods have been developed to detect this rearrangement and to study its prognostic significance. We report a novel four-color fluorescence in situ hybridization (FISH) assay that detects not only the typical TMPRSS2-ERG fusion but also alternative rearrangements of the TMPRSS2 or ERG gene. We validated this assay on fresh, frozen, or formalin-fixed paraffin-embedded prostate cancer specimens, including cell lines, primary prostate cancer tissues, xenograft tissues derived from metastatic prostate cancer, and metastatic tissues from castration-resistant prostate cancer (CRPC) patients. When compared with either reverse transcription-polymerase chain reaction or the Gen-Probe method as the technical reference, analysis using the four-color FISH assay demonstrated an analytical sensitivity of 94.5% (95% confidence interval [CI] 0.80-0.99) and specificity of 100% (95% CI 0.89-1.00) for detecting the TMPRSS2-ERG fusion. The TMPRSS2-ERG fusion was detected in 41% and 43% of primary prostate cancer (n = 59) and CRPC tumors (n = 82), respectively. Rearrangements other than the typical TMPRSS2-ERG fusion were confirmed by karyotype analysis and found in 7% of primary cancer and 13% of CRPC tumors. Successful karyotype analyses are reported for the first time on four of the xenograft samples, complementing the FISH results. Analysis using the four-color FISH assay provides sensitive detection of TMPRSS2 and ERG gene rearrangements in prostate cancer. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Qu, Xiaoyu AU - Qu X AD - Fred Hutchinson Cancer Research Center, Seattle, WA, USA. FAU - Randhawa, Grace AU - Randhawa G FAU - Friedman, Cynthia AU - Friedman C FAU - O'Hara-Larrivee, Siobhan AU - O'Hara-Larrivee S FAU - Kroeger, Kathleen AU - Kroeger K FAU - Dumpit, Ruth AU - Dumpit R FAU - True, Larry AU - True L FAU - Vakar-Lopez, Funda AU - Vakar-Lopez F FAU - Porter, Christopher AU - Porter C FAU - Vessella, Robert AU - Vessella R FAU - Nelson, Peter AU - Nelson P FAU - Fang, Min AU - Fang M LA - eng GR - P01 CA085859/CA/NCI NIH HHS/United States GR - P50 CA097186/CA/NCI NIH HHS/United States PT - Evaluation Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Validation Study DEP - 20130124 PL - United States TA - Cancer Genet JT - Cancer genetics JID - 101539150 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) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EC 3.4.21.- (TMPRSS2 protein, human) SB - IM MH - Animals MH - Carcinoma/diagnosis/*genetics/pathology MH - Cell Line, Tumor MH - Color MH - Humans MH - In Situ Hybridization, Fluorescence/*methods MH - Male MH - Neoplasm Metastasis MH - Oncogene Proteins, Fusion/*analysis/genetics MH - Prostatic Neoplasms/diagnosis/*genetics/pathology MH - Sensitivity and Specificity MH - Serine Endopeptidases/analysis/*genetics MH - Trans-Activators/analysis/*genetics MH - Transcriptional Regulator ERG MH - Translocation, Genetic/genetics MH - Transplantation, Heterologous PMC - PMC3632390 MID - NIHMS429656 EDAT- 2013/01/29 06:00 MHDA- 2013/04/13 06:00 PMCR- 2014/01/24 CRDT- 2013/01/29 06:00 PHST- 2012/11/02 00:00 [received] PHST- 2012/12/11 00:00 [revised] PHST- 2012/12/12 00:00 [accepted] PHST- 2013/01/29 06:00 [entrez] PHST- 2013/01/29 06:00 [pubmed] PHST- 2013/04/13 06:00 [medline] PHST- 2014/01/24 00:00 [pmc-release] AID - S2210-7762(12)00279-7 [pii] AID - 10.1016/j.cancergen.2012.12.004 [doi] PST - ppublish SO - Cancer Genet. 2013 Jan-Feb;206(1-2):1-11. doi: 10.1016/j.cancergen.2012.12.004. Epub 2013 Jan 24.