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Cancer Cell. 2014 Feb 10;25(2):152-65. doi: 10.1016/j.ccr.2014.01.009.

Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy.

Author information

1
Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
2
Computational Biology Division, Translational Genomics Research Institute, 445N, Fifth Street, Phoenix, AZ 85004, USA.
3
Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
4
Department of Medical Oncology, Thomas Jefferson University Hospital, 1025 Walnut Street, Suite 700, Philadelphia, PA 19107, USA.
5
Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas-Graduate School of Biomedical Sciences (GSBS) at Houston, Houston, TX 77030, USA.
6
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
7
Department of Bioinformatics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
8
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
9
Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas-Graduate School of Biomedical Sciences (GSBS) at Houston, Houston, TX 77030, USA. Electronic address: dmcconke@mdanderson.org.

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.

PMID:
24525232
PMCID:
PMC4011497
DOI:
10.1016/j.ccr.2014.01.009
[Indexed for MEDLINE]
Free PMC Article

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