MP83-14 GENOMIC EXPRESSION EVIDENCE FOR ANDROGEN RECEPTOR AXIS ACTIVATION IN UROTHELIAL CARCINOMA: DATA FROM THE CANCER GENOME ATLAS

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology IV1 Apr 2016MP83-14 GENOMIC EXPRESSION EVIDENCE FOR ANDROGEN RECEPTOR AXIS ACTIVATION IN UROTHELIAL CARCINOMA: DATA FROM THE CANCER GENOME ATLAS Edwin E. Morales, Stephen B. Williams, Jinesh G. Goodwin, Debasish Sundi, Carolyn L. Smith, David J. McConkey, and Ashish M. Kamat Edwin E. MoralesEdwin E. Morales More articles by this author , Stephen B. WilliamsStephen B. Williams More articles by this author , Jinesh G. GoodwinJinesh G. Goodwin More articles by this author , Debasish SundiDebasish Sundi More articles by this author , Carolyn L. SmithCarolyn L. Smith More articles by this author , David J. McConkeyDavid J. McConkey More articles by this author , and Ashish M. KamatAshish M. Kamat More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2196AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent investigations have implicated the androgen receptor in the oncogenesis and progression of urothelial carcinoma. Current evidence exists that inhibition of dihydrotestosterone (DHT) production decreases the risk of bladder cancer by nearly a third in a large North American cancer screening cohort. The precise biological mechanism of DHT inhibition and reduced bladder carcinogenesis remains to be elucidated. We sought to analyze the bladder database of the Cancer Genome Atlas (TCGA) for androgen gene signature enrichment, and for expression of downstream target genes of the androgen receptor using heat mapping and genome set enrichment analysis. METHODS The TCGA is a multicenter study that examined 11,000 patient tumors as well as normal tissues to generate a genetic atlas of 33 distinct cancer types. The bladder TCGA was queried for expression of androgen axis gene expression signatures using GENE-E software (Broad Institute, Cambridge MA). Using this data, gene expression patterns were analyzed and using hierarchical clustering, matched to existing TCGA basal and luminal tumor subtypes. RESULTS Expression of the 5-alpha reductase isozymes SRD5A1, 2, and 3 (the inhibitory target of finasteride) was confirmed using the 128 tumor TCGA database and clustered into basal and luminal TCGA subtypes, with Clusters 1 and 2 (luminal or “epithelial-like”) expressing SRD5A2 and 3 while basal and “p-53 like” tumors expressed the more typical prostatic SRD5A1. In addition, significant expression of steroidal pathway synthesis and androgen/estrogen axes genes were observed, again clustered by TCGA subtype. Validation of these preliminary findings are underway. CONCLUSIONS Gene expression data suggest that urothelial cancer of the bladder exhibits activation of androgen synthesis and androgen receptor cross-talk pathways along with expression of the enzyme 5-alpha reductase. Expression appears to segregate by TCGA subtype which may be important in future clinical trials for subtype-specific antitumor therapies. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1086 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Edwin E. Morales More articles by this author Stephen B. Williams More articles by this author Jinesh G. Goodwin More articles by this author Debasish Sundi More articles by this author Carolyn L. Smith More articles by this author David J. McConkey More articles by this author Ashish M. Kamat More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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