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Choi W , Porten S , Kim S , Willis D , Plimack ER , Hoffman-Censits J , Roth B , Cheng T , Tran M , Lee IL , Melquist J , Bondaruk J , Majewski T , Zhang S , Pretzsch S , Baggerly K , Siefker-Radtke A , Czerniak B , Dinney CP , McConkey DJ
Identification of distinct Basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy
Cancer Cell. 2014 Feb 10;25(2) :152-65
PMID: 24525232    PMCID: PMC4011497   
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Muscle-invasive bladder cancers (MIBCs) are biologically heterogeneous and have widely variable clinical outcomes and responses to conventional chemotherapy. We discovered three molecular subtypes of MIBC that resembled established molecular subtypes of breast cancer. Basal MIBCs shared biomarkers with basal breast cancers and were characterized by p63 activation, squamous differentiation, and more aggressive disease at presentation. Luminal MIBCs contained features of active PPARgamma and estrogen receptor transcription and were enriched with activating FGFR3 mutations and potential FGFR inhibitor sensitivity. p53-like MIBCs were consistently resistant to neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy, and all chemoresistant tumors adopted a p53-like phenotype after therapy. Our observations have important implications for prognostication, the future clinical development of targeted agents, and disease management with conventional chemotherapy.
Choi, Woonyoung Porten, Sima Kim, Seungchan Willis, Daniel Plimack, Elizabeth R Hoffman-Censits, Jean Roth, Beat Cheng, Tiewei Tran, Mai Lee, I-Ling Melquist, Jonathan Bondaruk, Jolanta Majewski, Tadeusz Zhang, Shizhen Pretzsch, Shanna Baggerly, Keith Siefker-Radtke, Arlene Czerniak, Bogdan Dinney, Colin P N McConkey, David J P30 CA016672/CA/NCI NIH HHS/United States P50 CA091846/CA/NCI NIH HHS/United States R01 CA151489/CA/NCI NIH HHS/United States United States Cancer Cell. 2014 Feb 10;25(2):152-65. doi: 10.1016/j.ccr.2014.01.009.