Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.

Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G, Cherniack AD, Hinoue T, Laird PW, Hoadley KA, Akbani R, Castro MAA, Gibb EA, Kanchi RS, Gordenin DA, Shukla SA, Sanchez-Vega F, Hansel DE, Czerniak BA, Reuter VE, Su X, de Sa Carvalho B, Chagas VS, Mungall KL, Sadeghi S, Pedamallu CS, Lu Y, Klimczak LJ, Zhang J, Choo C, Ojesina AI, Bullman S, Leraas KM, Lichtenberg TM, Wu CJ, Schultz N, Getz G, Meyerson M, Mills GB, McConkey DJ, TCGA Research Network, Weinstein JN, Kwiatkowski DJ, Lerner SP
Cell. 2017 171 (3): 540-556.e25

PMID: 28988769 · PMCID: PMC5687509 · DOI:10.1016/j.cell.2017.09.007

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.

Copyright © 2017 Elsevier Inc. All rights reserved.

MeSH Terms (11)

Aged Cluster Analysis DNA Methylation Humans MicroRNAs Middle Aged Muscle, Smooth RNA, Long Noncoding Survival Analysis Urinary Bladder Urinary Bladder Neoplasms

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