Comprehensive molecular characterization of muscle-invasive bladder cancer Journal Article


Authors: 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.
Article Title: 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. A multiplatform analysis of 412 muscle-invasive bladder cancer patients provides insights into mutational profiles with prognostic value and establishes a framework associating distinct tumor subtypes with clinical options. © 2017 Elsevier Inc.
Keywords: adult; cancer survival; controlled study; human tissue; aged; middle aged; survival analysis; gene cluster; gene mutation; genetics; microrna; cluster analysis; gene expression; cohort analysis; pathology; dna methylation; urinary bladder neoplasms; cancer genetics; messenger rna; carcinoma in situ; urinary bladder; micrornas; mutagenesis; muscle, smooth; smooth muscle; bladder; epithelial mesenchymal transition; muscle invasive bladder cancer; regulon; muscle-invasive bladder cancer; humans; human; male; female; priority journal; article; long untranslated rna; neoantigen; mutational load; rna, long noncoding; apobec mutation; basal mrna subtype; lncrna transcriptome; luminal mrna subtype; neuronal subtype; apolipoprotein b mrna editing enzyme catalytic polypeptide like
Journal Title: Cell
Volume: 171
Issue: 3
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2017-10-19
Start Page: 540
End Page: 556.e25
Language: English
DOI: 10.1016/j.cell.2017.09.007
PUBMED: 28988769
PROVIDER: scopus
PMCID: PMC5687509
DOI/URL:
Notes: Article -- Export Date: 1 December 2017 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Victor Reuter
    912 Reuter
  2. Nikolaus D Schultz
    202 Schultz