| Literature DB >> 28988769 |
A Gordon Robertson1, Jaegil Kim2, Hikmat Al-Ahmadie3, Joaquim Bellmunt4, Guangwu Guo5, Andrew D Cherniack2, Toshinori Hinoue6, Peter W Laird6, Katherine A Hoadley7, Rehan Akbani8, Mauro A A Castro9, Ewan A Gibb1, Rupa S Kanchi8, Dmitry A Gordenin10, Sachet A Shukla5, Francisco Sanchez-Vega11, Donna E Hansel12, Bogdan A Czerniak13, Victor E Reuter3, Xiaoping Su8, Benilton de Sa Carvalho14, Vinicius S Chagas9, Karen L Mungall1, Sara Sadeghi1, Chandra Sekhar Pedamallu2, Yiling Lu15, Leszek J Klimczak16, Jiexin Zhang8, Caleb Choo1, Akinyemi I Ojesina17, Susan Bullman2, Kristen M Leraas18, Tara M Lichtenberg18, Catherine J Wu19, Nicholaus Schultz11, Gad Getz2, Matthew Meyerson20, Gordon B Mills15, David J McConkey21, John N Weinstein22, David J Kwiatkowski23, Seth P Lerner24.
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.Entities:
Keywords: APOBEC mutation; DNA methylation; basal mRNA subtype; lncRNA transcriptome; luminal mRNA subtype; microRNA; muscle-invasive bladder cancer; neoantigen; neuronal subtype; regulon
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Year: 2017 PMID： 28988769 PMCID： PMC5687509 DOI： 10.1016/j.cell.2017.09.007
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582