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Identification of Distinct Basal and Luminal Subtypes of Muscle-Invasive Bladder Cancer with Different Sensitivities to Frontline 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 PN ; McConkey, David J

Cancer Cell, 2014-02, Vol.25 (2), p.152-165

eScholarship, University of California

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Título:
Identification of Distinct Basal and Luminal Subtypes of Muscle-Invasive Bladder Cancer with Different Sensitivities to Frontline Chemotherapy
Autor: 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 PN ; McConkey, David J
Assuntos: Aged ; Antineoplastic Combined Chemotherapy Protocols ; Basal Cell ; Biomarkers ; Blotting ; Breast Cancer ; Cancer ; Carcinoma ; Cell Differentiation ; Cell Proliferation ; Cisplatin ; Clinical Trials ; Cohort Studies ; Doxorubicin ; Drug Resistance ; Estrogen ; Female ; Fibroblast Growth Factor ; Gene Expression Profiling ; Genetics ; Humans ; Male ; Messenger ; Methotrexate ; MicroRNAs ; Muscle Neoplasms ; Mutation ; Neoadjuvant Therapy ; Neoplasm ; Neoplasm Invasiveness ; Neoplasm Staging ; Neurosciences ; Oncology & Carcinogenesis ; Oncology and Carcinogenesis ; Phase II as Topic ; PPAR gamma ; Prognosis ; Real-Time Polymerase Chain Reaction ; Receptor ; Receptors ; Reverse Transcriptase Polymerase Chain Reaction ; RNA ; Squamous Cell ; Tumor ; Tumor Suppressor Protein p53 ; Type 3 ; Urinary Bladder Neoplasms ; Urologic Diseases ; Vinblastine ; Western
É parte de: Cancer Cell, 2014-02, Vol.25 (2), p.152-165
Notas: Cancer Cell, vol 25, iss 2
152 - 165
Descrição: 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.
Editor: eScholarship, University of California
Idioma: Inglês

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

eScholarship, University of California

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