Identification of Distinct Basal and Luminal Subtypes of Muscle-Invasive Bladder Cancer with Different Sensitivities to Frontline Chemotherapy

Woonyoung Choi, Sima Porten, Seungchan Kim, Daniel Willis, Elizabeth R. Plimack, Jean Hoffman-Censits, Beat Roth, Tiewei Cheng, Mai Tran, I. Ling Lee, Jonathan Melquist, Jolanta Bondaruk, Tadeusz Majewski, Shizhen Zhang, Shanna Pretzsch, Keith Baggerly, Arlene Siefker-Radtke, Bogdan Czerniak, Colin P.N. Dinney, David J. McConkey

Research output: Contribution to journalArticle

Abstract

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 PPARγ 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.

Original languageEnglish (US)
Pages (from-to)152-165
Number of pages14
JournalCancer cell
Volume25
Issue number2
DOIs
StatePublished - Feb 10 2014
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Choi, W., Porten, S., Kim, S., Willis, D., Plimack, E. R., Hoffman-Censits, J., Roth, B., Cheng, T., Tran, M., Lee, I. L., Melquist, J., Bondaruk, J., Majewski, T., Zhang, S., Pretzsch, S., Baggerly, K., Siefker-Radtke, A., Czerniak, B., Dinney, C. P. N., & McConkey, D. J. (2014). Identification of Distinct Basal and Luminal Subtypes of Muscle-Invasive Bladder Cancer with Different Sensitivities to Frontline Chemotherapy. Cancer cell, 25(2), 152-165. https://doi.org/10.1016/j.ccr.2014.01.009