You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 2015MP6-09 MOLECULAR AND CLINICAL CHARACTERIZATION OF 1,577 PRIMARY PROSTATE CANCER TUMORS REVEALS NOVEL CLINICAL AND BIOLOGICAL INSIGHTS INTO ITS SUBTYPES Scott Tomlins, Mohammed Alshalalfa, Nicholas Erho, Kasra Yousefi, Shuang Zhao, robert den, adam dicker, bruce trock, Angelo Demarzo, Ashley Ross, Edward Schaeffer, Erick Klein, Cristina Magi-Galluzzi, jeffery karnes, Rober Jenkins, elai davicioni, and Felix Feng Scott TomlinsScott Tomlins More articles by this author , Mohammed AlshalalfaMohammed Alshalalfa More articles by this author , Nicholas ErhoNicholas Erho More articles by this author , Kasra YousefiKasra Yousefi More articles by this author , Shuang ZhaoShuang Zhao More articles by this author , robert denrobert den More articles by this author , adam dickeradam dicker More articles by this author , bruce trockbruce trock More articles by this author , Angelo DemarzoAngelo Demarzo More articles by this author , Ashley RossAshley Ross More articles by this author , Edward SchaefferEdward Schaeffer More articles by this author , Erick KleinErick Klein More articles by this author , Cristina Magi-GalluzziCristina Magi-Galluzzi More articles by this author , jeffery karnesjeffery karnes More articles by this author , Rober JenkinsRober Jenkins More articles by this author , elai davicionielai davicioni More articles by this author , and Felix FengFelix Feng More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.256AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer molecular subtypes based on ETS gene fusions and SPINK1 were originally identified through distinct gene expression profiles. Such molecular subtypes may have utility in disease stratification and clonality assessment, complementing available purely prognostic tests. Hence, we determined the analytical validity of molecular subtyping and explored clinical associations using global gene expression profiles in a large cohort of PCa METHODS We analyzed 1,577 patient Affymetrix Human Exon 1.0ST GeneChip expression profiles from 8 radical prostatectomy (RP) cohorts; 5 of them generated as part of the Decipher® platform for the Decipher® discovery or validation. Multi-feature random forest classifiers and outlier analysis were used to define microarray-based molecular subtypes and characterize clinical associations. RESULTS A random forest (RF) classifier (m-ERG) was trained and validated to predict ERG fusion status using separate subsets of a single-institution RP cohort (total n=407) with known ERG rearrangement status defined by FISH, achieving >95% sensitivity and specificity in the validation subset. The model was then applied to 7 independent RP cohorts to predict ERG rearrangement status. Less frequent rearrangements involving other ETS genes (ETV1, ETV4, ETV5, FLI1) or SPINK1 over-expression were predicted based on gene expression outlier analysis. Across cohorts, 45%, 9% 8% and 38% of PCa were classified as ERG+, ERGγ2;ETS+, ERGγ2;SPINK+, and Triple Negative (ERGγ2;/ETSγ2;/SPINK1γ2;), respectively. Global gene expression analysis shows that the four subtypes could be collapsed into three entities (ERG+, ERGγ2;ETS+ and SPINK+/Triple Negative) based on expression patterns and clinical characteristics similarity. Based on multivariable analysis, ERG+ is significantly associated with lower pre-PSA (p<0.001), lower Gleason score (p<0.001), the presence of extraprostatic extension (p<0.001) and European Americans (p<0.001), but not associated with outcome. ERGγ2;ETS+ is significantly associated with SVI (p=0.01) and ERGγ2;SPINK+ is enriched in African Americans (p<0.001). CONCLUSIONS The Decipher® platform can accurately determine ERG rearrangement status and PCa molecular subtypes. Inclusion of molecular subtyping, such as m-ERG status, may enable additional precision medicine opportunities in prognostic tests and provides insights into the development of novel therapeutic approaches. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e57 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Scott Tomlins More articles by this author Mohammed Alshalalfa More articles by this author Nicholas Erho More articles by this author Kasra Yousefi More articles by this author Shuang Zhao More articles by this author robert den More articles by this author adam dicker More articles by this author bruce trock More articles by this author Angelo Demarzo More articles by this author Ashley Ross More articles by this author Edward Schaeffer More articles by this author Erick Klein More articles by this author Cristina Magi-Galluzzi More articles by this author jeffery karnes More articles by this author Rober Jenkins More articles by this author elai davicioni More articles by this author Felix Feng More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...