TY - JOUR
T1 - Identification of Distinct Basal and Luminal Subtypes of Muscle-Invasive Bladder Cancer with Different Sensitivities to Frontline Chemotherapy
AU - Choi, Woonyoung
AU - Porten, Sima
AU - Kim, Seungchan
AU - Willis, Daniel
AU - Plimack, Elizabeth R.
AU - Hoffman-Censits, Jean
AU - Roth, Beat
AU - Cheng, Tiewei
AU - Tran, Mai
AU - Lee, I. Ling
AU - Melquist, Jonathan
AU - Bondaruk, Jolanta
AU - Majewski, Tadeusz
AU - Zhang, Shizhen
AU - Pretzsch, Shanna
AU - Baggerly, Keith
AU - Siefker-Radtke, Arlene
AU - Czerniak, Bogdan
AU - Dinney, Colin P.N.
AU - McConkey, David J.
N1 - Funding Information:
The authors would like to acknowledge Lyndsay Harris (Southwest Oncology Group, Breast Committee, Case Cancer Center) for her help with the DASL assay and Neema Navai and Matthew Wszolek for sharing their miR-200b and miR-200c PCR data. This work was supported by a grant from the Baker Foundation, the MD Anderson Bladder SPORE (P50 CA91846), grant R01 CA151489 (to B.C.), and the MD Anderson CCSG (P30 016672). E.R.P. is supported by grant no. IRG-92-027-17 from the American Cancer Society. This paper is dedicated to the memory of Dexter Baker. The authors wish to disclose that the MD Anderson Cancer Center has submitted a patent that covers some of the findings reported in this manuscript.
PY - 2014/2/10
Y1 - 2014/2/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ccr.2014.01.009
DO - 10.1016/j.ccr.2014.01.009
M3 - Article
C2 - 24525232
AN - SCOPUS:84893520397
SN - 1535-6108
VL - 25
SP - 152
EP - 165
JO - Cancer cell
JF - Cancer cell
IS - 2
ER -