Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

Cell. 2017 Oct 19;171(3):540-556.e25. doi: 10.1016/j.cell.2017.09.007. Epub 2017 Oct 5.

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.

Keywords: APOBEC mutation; DNA methylation; basal mRNA subtype; lncRNA transcriptome; luminal mRNA subtype; microRNA; muscle-invasive bladder cancer; neoantigen; neuronal subtype; regulon.

MeSH terms

  • Aged
  • Cluster Analysis
  • DNA Methylation
  • Humans
  • MicroRNAs / genetics
  • Middle Aged
  • Muscle, Smooth / pathology
  • RNA, Long Noncoding / genetics
  • Survival Analysis
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / epidemiology
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology*
  • Urinary Bladder Neoplasms / therapy

Substances

  • MicroRNAs
  • RNA, Long Noncoding

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