MP61-07 IDENTIFICATION OF DISTINCT BASAL AND LUMINAL SUBSETS OF HUMAN BLADDER CANCERS WITH DIFFERENT SENSITIVITIES TO FRONTLINE CHEMOTHERAPY

Abstract

You have accessJournal of UrologyBladder Cancer: Invasive IV1 Apr 2014MP61-07 IDENTIFICATION OF DISTINCT BASAL AND LUMINAL SUBSETS OF HUMAN BLADDER CANCERS WITH DIFFERENT SENSITIVITIES TO FRONTLINE CHEMOTHERAPY Woonyoung Choi, Sima Porten, Seungchan Kim, Beat Roth, Teiwei Chang, Daniel Willis, Mai Tran, I-Ling Lee, Jonathan Melquist, Jolanta Bondaruk, Tadeusz Majewski, Shizhen Zhang, Shanna Pretzsch, Keith Baggerly, Elizabeth Plimack, Jean Hoffman-Censits, Arlene Siefker-Radtke, Bogdan Czerniak, Colin Dinney, and David McConkey Woonyoung ChoiWoonyoung Choi More articles by this author , Sima PortenSima Porten More articles by this author , Seungchan KimSeungchan Kim More articles by this author , Beat RothBeat Roth More articles by this author , Teiwei ChangTeiwei Chang More articles by this author , Daniel WillisDaniel Willis More articles by this author , Mai TranMai Tran More articles by this author , I-Ling LeeI-Ling Lee More articles by this author , Jonathan MelquistJonathan Melquist More articles by this author , Jolanta BondarukJolanta Bondaruk More articles by this author , Tadeusz MajewskiTadeusz Majewski More articles by this author , Shizhen ZhangShizhen Zhang More articles by this author , Shanna PretzschShanna Pretzsch More articles by this author , Keith BaggerlyKeith Baggerly More articles by this author , Elizabeth PlimackElizabeth Plimack More articles by this author , Jean Hoffman-CensitsJean Hoffman-Censits More articles by this author , Arlene Siefker-RadtkeArlene Siefker-Radtke More articles by this author , Bogdan CzerniakBogdan Czerniak More articles by this author , Colin DinneyColin Dinney More articles by this author , and David McConkeyDavid McConkey More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1884AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Muscle-invasive bladder cancers (MIBCs) are a heterogeneous group of tumors that display widely variable clinical outcomes and responses to conventional chemotherapy. METHODS We used whole genome mRNA expression profiling and unsupervised hierarchical cluster analyses on a cohort of 73 flash frozen primary tumors to identify 3 distinct subsets of muscle-invasive bladder cancer (MIBC). We confirmed the existence of these 3 subsets in a second cohort of 57 formalin-fixed, paraffin-embedded (FFPE) MIBCs and in 2 other public datasets. RESULTS The first “basal” subset of MIBCs shared biomarkers with basal/triple negative breast cancers, expressed EMT markers, an active "basal" EGFR-STAT3-p63 transcriptional network, and displayed squamous differentiation. These basal cancers presented at a later stage and were associated with poor clinical outcomes. A third “luminal” subset expressed estrogen receptor and PPARγ gene signatures, luminal breast differentiation markers, and activating FGFR3 mutations. Luminal BC cell lines were sensitive to FGFR3 inhibition. The second subset was characterized by active p53 pathway activation. p53-like MIBCs also contained luminal biomarkers, were infiltrated with stromal cells, and were resistant to neoadjuvant cisplatin-based chemotherapy. CONCLUSIONS Molecular subtyping of MIBCs can be used to identify lethal cancers.The observation that bladder and breast cancers share significant features has implications for prognostication and the development of targeted therapies. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e685 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Woonyoung Choi More articles by this author Sima Porten More articles by this author Seungchan Kim More articles by this author Beat Roth More articles by this author Teiwei Chang More articles by this author Daniel Willis More articles by this author Mai Tran More articles by this author I-Ling Lee More articles by this author Jonathan Melquist More articles by this author Jolanta Bondaruk More articles by this author Tadeusz Majewski More articles by this author Shizhen Zhang More articles by this author Shanna Pretzsch More articles by this author Keith Baggerly More articles by this author Elizabeth Plimack More articles by this author Jean Hoffman-Censits More articles by this author Arlene Siefker-Radtke More articles by this author Bogdan Czerniak More articles by this author Colin Dinney More articles by this author David McConkey More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...