[PDF][PDF] Comprehensive molecular characterization of muscle-invasive bladder cancer

AG Robertson, J Kim, H Al-Ahmadie, J Bellmunt, G Guo… - Cell, 2017 - cell.com
Cell, 2017cell.com
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 …
Summary
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.
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