Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis.

Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.

Cell. 2017 Oct 04 [Epub ahead of print]

A Gordon Robertson, Jaegil Kim, Hikmat Al-Ahmadie, Joaquim Bellmunt, Guangwu Guo, Andrew D Cherniack, Toshinori Hinoue, Peter W Laird, Katherine A Hoadley, Rehan Akbani, Mauro A A Castro, Ewan A Gibb, Rupa S Kanchi, Dmitry A Gordenin, Sachet A Shukla, Francisco Sanchez-Vega, Donna E Hansel, Bogdan A Czerniak, Victor E Reuter, Xiaoping Su, Benilton de Sa Carvalho, Vinicius S Chagas, Karen L Mungall, Sara Sadeghi, Chandra Sekhar Pedamallu, Yiling Lu, Leszek J Klimczak, Jiexin Zhang, Caleb Choo, Akinyemi I Ojesina, Susan Bullman, Kristen M Leraas, Tara M Lichtenberg, Catherine J Wu, Nicholaus Schultz, Gad Getz, Matthew Meyerson, Gordon B Mills, David J McConkey, TCGA Research Network , John N Weinstein, David J Kwiatkowski, Seth P Lerner

Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada., Cancer Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., PSMAR-IMIM Lab, Bladder Cancer Center, Department of Medicine, Dana-Farber Cancer Institute and Harvard University, Boston, MA 02215, USA., Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard University, Boston, MA 02115, USA., Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA., Department of Genetics, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA., Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Bioinformatics and Systems Biology Laboratory, Federal University of Paraná Polytechnic Center, Curitiba, PR CEP 80.060-000, Brazil., Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA., Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Department of Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA., Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Biostatistics and Computational Biology Laboratory, Department of Statistics, University of Campinas, São Paulo, 13.083-859, Brazil., Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA., Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Biospecimen Core Resource, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA., Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Pathology and Medical Oncology, Dana-Farber Cancer Institute and Harvard University, Boston, MA 02115, USA., Greenberg Bladder Cancer Institute, Johns Hopkins University, Baltimore, MD 21218, USA., Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA. Electronic address: ., Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: ., Scott Department of Urology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: .

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