Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

Academic Article

Abstract

  • © 2017 Elsevier Inc. 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.
  • Published In

  • Cell  Journal
  • Digital Object Identifier (doi)

    Author List

  • Robertson AG; Kim J; Al-Ahmadie H; Bellmunt J; Guo G; Cherniack AD; Hinoue T; Laird PW; Hoadley KA; Akbani R
  • Start Page

  • 540
  • End Page

  • 556.e25
  • Volume

  • 171
  • Issue

  • 3