Genomic Subtypes of Non-invasive Bladder Cancer with Distinct Metabolic Profile and Female Gender Bias in KDM6A Mutation Frequency

Carolyn D Hurst, Olivia Alder, Fiona M Platt, Alastair Droop, Lucy F Stead, Julie E Burns, George J Burghel, Sunjay Jain, Leszek J Klimczak, Helen Lindsay, Jo-An Roulson, Claire F Taylor, Helene Thygesen, Angus J Cameron, Anne J Ridley, Helen R Mott, Dmitry A Gordenin, Margaret A Knowles

Research output: Contribution to journalArticle (Academic Journal)

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Abstract

Bladder cancer incurs a higher lifetime treatment cost than other cancers due to frequent recurrence of non-invasive disease. Improved prognostic biomarkers and localized therapy are needed for this large patient group. We defined two major genomic subtypes of primary stage Ta tumors. One of these was characterized by loss of 9q including TSC1, increased KI67 labeling index, upregulated glycolysis, DNA repair, mTORC1 signaling, features of the unfolded protein response, and altered cholesterol homeostasis. Comparison with muscle-invasive bladder cancer mutation profiles revealed lower overall mutation rates and more frequent mutations in RHOB and chromatin modifier genes. More mutations in the histone lysine demethylase KDM6A were present in non-invasive tumors from females than males.

Original languageEnglish
Pages (from-to)701-715.e7
Number of pages22
JournalCancer Cell
Volume32
Issue number5
Early online date13 Nov 2017
DOIs
Publication statusPublished - 13 Nov 2017

Keywords

  • Carcinoma, Transitional Cell
  • Cell Line, Tumor
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Frequency
  • Genomics
  • HEK293 Cells
  • Histone Demethylases
  • Humans
  • Male
  • Metabolome
  • Metabolomics
  • Mutation
  • Nuclear Proteins
  • Sex Factors
  • Urinary Bladder Neoplasms
  • Journal Article

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