Cancer cell · 2017
Genomic Subtypes of Non-invasive Bladder Cancer with Distinct Metabolic Profile and Female Gender Bias in KDM6A Mutation Frequency.
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Hurst Carolyn D, Alder Olivia, Platt Fiona M, Droop Alastair, Stead Lucy F, Burns Julie E, Burghel George J, Jain Sunjay, Klimczak Leszek J, Lindsay Helen, Roulson Jo-An, Taylor Claire F, Thygesen Helene, Cameron Angus J, Ridley Anne J, Mott Helen R, Gordenin Dmitry A, Knowles Margaret A
Аннотация
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.