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

Autor: Mohammad Asim, Silvia Halim, Martin Mørck Mortensen, Hayley C. Whitaker, Adele Murrell, Anne Y. Warren, Simon A. Gayther, Alastair D. Lamb, Ian G. Mills, Jonathan D. Kay, Stephen J. Ball, Sebastian M. Armasu, Antonio Ramos-Montoya, Karina Dalsgaard Sørensen, Siri H. Strand, Claire M. Wells, Michael Borre, Kathryn Woodfine, Melissa C. Larson, Charles E. Massie, Kate Lawrenson, Ellen L. Goode, David E. Neal, Roslin Russell, Torben F. Ørntoft, Brooke L. Fridley, John R. W. Masters, Helen Ross-Adams
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
HNF1B
Genome-wide association study
Linkage Disequilibrium
Prostate cancer
0302 clinical medicine
Cell Movement
Gene Regulatory Networks
Promoter Regions
Genetic
Cancer
EQTL
Regulation of gene expression
Genetics
Ovarian Neoplasms
prostate
Prostate
HNF1B Gene
3. Good health
Gene Expression Regulation
Neoplastic
Oncology
Ovarian
030220 oncology & carcinogenesis
DNA methylation
Female
Research Paper
Risk
Epithelial-Mesenchymal Transition
Genotype
Biology
eQTL
Polymorphism
Single Nucleotide
03 medical and health sciences
SDG 3 - Good Health and Well-being
Cell Line
Tumor
Journal Article
medicine
ovarian
cancer
Humans
Genetic Predisposition to Disease
Epigenetics
Alleles
Cell Proliferation
Hepatocyte Nuclear Factor 1-beta
Genetic Variation
Prostatic Neoplasms
DNA Methylation
medicine.disease
030104 developmental biology
Cancer research
Genome-Wide Association Study
Zdroj: Ross-Adams, H, Ball, S, Lawrenson, K, Halim, S, Russell, R, Wells, C, Strand, S H, Ørntoft, T F, Larson, M, Armasu, S, Massie, C E, Asim, M, Mortensen, M M, Borre, M, Woodfine, K, Warren, A Y, Lamb, A D, Kay, J, Whitaker, H, Ramos-Montoya, A, Murrell, A, Sørensen, K D, Fridley, B L, Goode, E L, Gayther, S A, Masters, J, Neal, D E & Mills, I G 2016, ' HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer ', Oncotarget, vol. 7, no. 46, pp. 74734-74746 . https://doi.org/10.18632/oncotarget.12543
Ross-Adams, H, Ball, S, Lawrenson, K, Halim, S, Russell, R, Wells, C, Strand, S H, Ørntoft, T F, Larson, M, Armasu, S, Massie, C E, Asim, M, Mortensen, M M, Borre, M, Woodfine, K, Warren, A Y, Lamb, A D, Kay, J, Whitaker, H, Ramos-Montoya, A, Murrell, A, Sørensen, K D, Fridley, B L, Goode, E L, Gayther, S A, Masters, J, Neal, D E & Mills, I G 2016, ' HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer ', Oncotarget . https://doi.org/10.18632/oncotarget.12543
Oncotarget
Ross-Adams, H, Ball, S J, Lawrenson, K, Halim, S, Russell, R, Wells, C, Strand, S, Ørntoft, T F, Larson, M C, Armasu, S M, Massie, C E, Asim, M, Mortensen, M M, Borre, M, Woodfine, K, Warren, A Y, Lamb, A D, Kay, J, Whitaker, H, Ramos-Montoya, A, Murrell, A, Sørensen, K D, Fridley, B L, Goode, E L, Gayther, S A, Masters, J R, Neal, D E & Mills, I G 2016, ' HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer ', OncoTarget, vol. 7, no. 46, pp. 74734-74746 . https://doi.org/10.18632/oncotarget.12543
DOI: 10.18632/oncotarget.12543
Popis: 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.
Databáze: OpenAIRE
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