STANDARD_NAME SETLUR_PROSTATE_CANCER_TMPRSS2_ERG_FUSION_UP SYSTEMATIC_NAME M3695 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/SETLUR_PROSTATE_CANCER_TMPRSS2_ERG_FUSION_UP NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes up-regulated in prostate cancer samples bearing the fusion of TMPRSS2 with ERG [GeneID=7113;2078]. DESCRIPTION_FULL BACKGROUND: The majority of prostate cancers harbor gene fusions of the 5'-untranslated region of the androgen-regulated transmembrane protease serine 2 (TMPRSS2) promoter with erythroblast transformation-specific transcription factor family members. The common fusion between TMPRESS2 and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) is associated with a more aggressive clinical phenotype, implying the existence of a distinct subclass of prostate cancer defined by this fusion. METHODS: We used complementary DNA-mediated annealing, selection, ligation, and extension to determine the expression profiles of 6144 transcriptionally informative genes in archived biopsy samples from 455 prostate cancer patients in the Swedish Watchful Waiting cohort (1987-1999) and the United States-based Physicians(') Health Study cohort (1983-2003). A gene expression signature for prostate cancers with the TMPRSS2-ERG fusion was determined using partitioning and classification models and used in computational functional analysis. Cell proliferation and TMPRSS2-ERG expression in androgen receptor-negative (NCI-H660) prostate cancer cells after treatment with vehicle or estrogenic compounds were assessed by viability assays and quantitative polymerase chain reaction, respectively. All statistical tests were two-sided. RESULTS: We identified an 87-gene expression signature that distinguishes TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity (area under the curve = 0.80, 95% confidence interval [CI] = 0.792 to 0.81; P < .001). Computational analysis suggested that this fusion signature was associated with estrogen receptor (ER) signaling. Viability of NCI-H660 cells decreased after treatment with estrogen (viability normalized to day 0, estrogen vs vehicle at day 8, mean = 2.04 vs 3.40, difference = 1.36, 95% CI = 1.12 to 1.62) or ERbeta agonist (ERbeta agonist vs vehicle at day 8, mean = 1.86 vs 3.40, difference = 1.54, 95% CI = 1.39 to 1.69) but increased after ERalpha agonist treatment (ERalpha agonist vs vehicle at day 8, mean = 4.36 vs 3.40, difference = 0.96, 95% CI = 0.68 to 1.23). Similarly, expression of TMPRSS2-ERG decreased after ERbeta agonist treatment (fold change over internal control, ERbeta agonist vs vehicle at 24 hours, NCI-H660, mean = 0.57- vs 1.0-fold, difference = 0.43-fold, 95% CI = 0.29- to 0.57-fold) and increased after ERalpha agonist treatment (ERalpha agonist vs vehicle at 24 hours, mean = 5.63- vs 1.0-fold, difference = 4.63-fold, 95% CI = 4.34- to 4.92-fold). CONCLUSIONS: TMPRSS2-ERG fusion prostate cancer is a distinct molecular subclass. TMPRSS2-ERG expression is regulated by a novel ER-dependent mechanism. PMID 18505969 GEOID GSE8402 AUTHORS Setlur SR,Mertz KD,Hoshida Y,Demichelis F,Lupien M,Perner S,Sboner A,Pawitan Y,Andrén O,Johnson LA,Tang J,Adami HO,Calza S,Chinnaiyan AM,Rhodes D,Tomlins S,Fall K,Mucci LA,Kantoff PW,Stampfer MJ,Andersson SO,Varenhorst E,Johansson JE,Brown M,Golub TR,Rubin MA CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 3: Expression level=Increased FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS ABCC8,ALDH18A1,AMPD3,ARHGAP29,ARHGDIB,BAG5,BMPR1B,CACNA1D,CADPS,COL9A2,CPSF6,CRISP3,DBN1,DDEF2,ECE1,EIF4G3,EIF5,ERG,GHR,GP1BB,HDAC1,KCNN2,KHDRBS3,KIAA0247,KNS2,LRP1,MAP2K5,MAP3K5,MAP7,MLXIP,MTA1,MYO6,NCOA1,NDUFS5,OCLN,PCDHGB7,PDE9A,PEX10,PFTK1,PGD,PLA2G7,PRKAR1B,PRKCBP1,PSMD13,PTK7,PTPRK,RAB30,RAGE,RFX1,RGS10,RPP38,SAFB,SEPT9,SH3YL1,SIPA1L1,SMARCD1,SNRPB2,TBP,TFDP1,THUMPD1,TLE1,TPP2,TWIST1,UBE2G1,UGDH,XRCC5,ZNF3 GENE_SYMBOLS ABCC8,ALDH18A1,AMPD3,ARHGAP29,ARHGDIB,BAG5,BMPR1B,CACNA1D,CADPS,COL9A2,CPSF6,CRISP3,DBN1,ASAP2,ECE1,EIF4G3,EIF5,ERG,GHR,GP1BB,HDAC1,KCNN2,KHDRBS3,SUSD6,KLC1,LRP1,MAP2K5,MAP3K5,MAP7,MLXIP,MTA1,MYO6,NCOA1,NDUFS5,OCLN,PCDHGB7,PDE9A,PEX10,CDK14,PGD,PLA2G7,PRKAR1B,ZMYND8,PSMD13,PTK7,PTPRK,RAB30,MOK,RFX1,RGS10,RPP38,SAFB,SEPTIN9,SH3YL1,SIPA1L1,SMARCD1,SNRPB2,TBP,TFDP1,THUMPD1,TLE1,TPP2,TWIST1,UBE2G1,UGDH,XRCC5,ZNF3 FOUNDER_NAMES