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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.

SUBMITTER: Robertson AG 

PROVIDER: S-EPMC5687509 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.

Robertson A Gordon AG   Kim Jaegil J   Al-Ahmadie Hikmat H   Bellmunt Joaquim J   Guo Guangwu G   Cherniack Andrew D AD   Hinoue Toshinori T   Laird Peter W PW   Hoadley Katherine A KA   Akbani Rehan R   Castro Mauro A A MAA   Gibb Ewan A EA   Kanchi Rupa S RS   Gordenin Dmitry A DA   Shukla Sachet A SA   Sanchez-Vega Francisco F   Hansel Donna E DE   Czerniak Bogdan A BA   Reuter Victor E VE   Su Xiaoping X   de Sa Carvalho Benilton B   Chagas Vinicius S VS   Mungall Karen L KL   Sadeghi Sara S   Pedamallu Chandra Sekhar CS   Lu Yiling Y   Klimczak Leszek J LJ   Zhang Jiexin J   Choo Caleb C   Ojesina Akinyemi I AI   Bullman Susan S   Leraas Kristen M KM   Lichtenberg Tara M TM   Wu Catherine J CJ   Schultz Nicholaus N   Getz Gad G   Meyerson Matthew M   Mills Gordon B GB   McConkey David J DJ   Weinstein John N JN   Kwiatkowski David J DJ   Lerner Seth P SP  

Cell 20171005 3


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 sm  ...[more]

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