Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.

Abstract

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.

• Authors: 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
• Journal: Cell (Cell) Vol. 171 Issue 3 Pg. 540-556.e25 (Oct 19 2017) ISSN: 1097-4172 [Electronic] United States
• PMID: 28988769 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• MicroRNAs
• RNA, Long Noncoding

Topics

• Aged
• Cluster Analysis
• DNA Methylation
• Humans
• MicroRNAs (genetics)
• Middle Aged
• Muscle, Smooth (pathology)
• RNA, Long Noncoding (genetics)
• Survival Analysis
• Urinary Bladder (pathology)
• Urinary Bladder Neoplasms (epidemiology, genetics, pathology, therapy)