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HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer.

Whitaker, HC; Ross-Adams, H; Ball, S; Lawrensen, K; Halim, S; Russell, R; Wells, C; ... Mills, IG; + view all (2016) HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer. Oncotarget 10.18632/oncotarget.12543. Green open access

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Abstract

Two independent regions within HNF1B are consistently identified in prostate and ovarian cancer genome-wide association studies (GWAS); their functional roles are unclear. We link prostate cancer (PC) risk SNPs rs11649743 and rs3760511 with elevated HNF1B gene expression and allele-specific epigenetic silencing, and outline a mechanism by which common risk variants could effect functional changes that increase disease risk: functional assays suggest that HNF1B is a pro-differentiation factor that suppresses epithelial-to-mesenchymal transition (EMT) in unmethylated, healthy tissues. This tumor-suppressor activity is lost when HNF1B is silenced by promoter methylation in the progression to PC. Epigenetic inactivation of HNF1B in ovarian cancer also associates with known risk SNPs, with a similar impact on EMT. This represents one of the first comprehensive studies into the pleiotropic role of a GWAS-associated transcription factor across distinct cancer types, and is the first to describe a conserved role for a multi-cancer genetic risk factor.

Type: Article
Title: HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer.
Open access status: An open access version is available from UCL Discovery
DOI: 10.18632/oncotarget.12543
Publisher version: http://dx.doi.org/10.18632/oncotarget.12543
Language: English
Additional information: Copyright © 2016 Impact Journals, LLC. All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License (CC BY 3.0) (https://creativecommons.org/licenses/by/3.0/)
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
URI: https://discovery.ucl.ac.uk/id/eprint/1521979
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