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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2017 Nov 15

PMID 29136510

Citations 143

Authors

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

Affiliations

Soon will be listed here.

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.

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