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

doi:10.1016/j.ccell.2017.08.005

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 journal › Article › peer-review

208 Citations (Scopus)

Abstract

Summary 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 language	English
Article number	e7
Pages (from-to)	701-715
Journal	CANCER CELL
Volume	32
Issue number	5
Early online date	13 Nov 2017
DOIs	https://doi.org/10.1016/j.ccell.2017.08.005
Publication status	E-pub ahead of print - 13 Nov 2017

Keywords

bladder cancer
genomics
subtypes
recurrence-free survival
mTORC1
metabolism
gender
KDM6A
RHOB

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccell.2017.08.005

https://www.sciencedirect.com/science/article/pii/S1535610817303483

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Hurst, C. D., Alder, O., Platt, F. M., Droop, A., Stead, L. F., Burns, J. E., Burghel, G. J., Jain, S., Klimczak, L. J., Lindsay, H., Roulson, J.-A., Taylor, C. F., Thygesen, H., Cameron, A. J., Ridley, A. J., Mott, H. R., Gordenin, D. A., & Knowles, M. A. (2017). Genomic Subtypes of Non-invasive Bladder Cancer with Distinct Metabolic Profile and Female Gender Bias in KDM6A Mutation Frequency. CANCER CELL, 32(5), 701-715. Article e7. Advance online publication. https://doi.org/10.1016/j.ccell.2017.08.005

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

abstract = "Summary 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.",

keywords = "bladder cancer, genomics, subtypes, recurrence-free survival, mTORC1, metabolism, gender, KDM6A, RHOB",

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

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doi = "10.1016/j.ccell.2017.08.005",

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Hurst, CD, Alder, O, Platt, FM, Droop, A, Stead, LF, Burns, JE, Burghel, GJ, Jain, S, Klimczak, LJ, Lindsay, H, Roulson, J-A, Taylor, CF, Thygesen, H, Cameron, AJ, Ridley, AJ, Mott, HR, Gordenin, DA & Knowles, MA 2017, 'Genomic Subtypes of Non-invasive Bladder Cancer with Distinct Metabolic Profile and Female Gender Bias in KDM6A Mutation Frequency', CANCER CELL, vol. 32, no. 5, e7, pp. 701-715. https://doi.org/10.1016/j.ccell.2017.08.005

TY - JOUR

T1 - Genomic Subtypes of Non-invasive Bladder Cancer with Distinct Metabolic Profile and Female Gender Bias in KDM6A Mutation Frequency

AU - Hurst, Carolyn D.

AU - Alder, Olivia

AU - Platt, Fiona M.

AU - Droop, Alastair

AU - Stead, Lucy F.

AU - Burns, Julie E.

AU - Burghel, George J.

AU - Jain, Sunjay

AU - Klimczak, Leszek J.

AU - Lindsay, Helen

AU - Roulson, Jo-An

AU - Taylor, Claire F.

AU - Thygesen, Helene

AU - Cameron, Angus J.

AU - Ridley, Anne J.

AU - Mott, Helen R.

AU - Gordenin, Dmitry A.

AU - Knowles, Margaret A.

PY - 2017/11/13

Y1 - 2017/11/13

N2 - Summary 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.

AB - Summary 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.

KW - bladder cancer

KW - genomics

KW - subtypes

KW - recurrence-free survival

KW - mTORC1

KW - metabolism

KW - gender

KW - KDM6A

KW - RHOB

U2 - 10.1016/j.ccell.2017.08.005

DO - 10.1016/j.ccell.2017.08.005

M3 - Article

SN - 1535-6108

VL - 32

SP - 701

EP - 715

JO - CANCER CELL

JF - CANCER CELL

IS - 5

M1 - e7

ER -

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

Abstract

Keywords

UN SDGs

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