Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer
- Robertson, A.G.
- Kim, J.
- Al-Ahmadie, H.
- Bellmunt, J.
- Guo, G.
- Cherniack, A.D.
- Hinoue, T.
- Laird, P.W.
- Hoadley, K.A.
- Akbani, R.
- Castro, M.A.A.
- Gibb, E.A.
- Kanchi, R.S.
- Gordenin, D.A.
- Shukla, S.A.
- Sanchez-Vega, F.
- Hansel, D.E.
- Czerniak, B.A.
- Reuter, V.E.
- Su, X.
- de Sa Carvalho, B.
- Chagas, V.S.
- Mungall, K.L.
- Sadeghi, S.
- Pedamallu, C.S.
- Lu, Y.
- Klimczak, L.J.
- Zhang, J.
- Choo, C.
- Ojesina, A.I.
- Bullman, S.
- Leraas, K.M.
- Lichtenberg, T.M.
- Wu, C.J.
- Schultz, N.
- Getz, G.
- Meyerson, M.
- Mills, G.B.
- McConkey, D.J.
- TCGA Research Network
- Weinstein, J.N.
- Kwiatkowski, D.J.
- Lerner, S.P.
DOIAbstract
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 ...
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