HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer
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 epigenet...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Rapamycin Press
2016
|
| _version_ | 1797089157315559424 |
|---|---|
| author | Ross-Adams, H Ball, S Lawrenson, K Halim, S Russell, R Wells, C Strand, SH Ørntoft, TF Larson, M Armasu, S Massie, CE Asim, M Mortensen, MM Borre, M Woodfine, K Warren, AY Lamb, AD Kay, J Whitaker, H Ramos-Montoya, A Murrell, A Sørensen, KD Fridley, BL Goode, EL Gayther, SA Masters, J Neal, DE Mills, IG |
| author_facet | Ross-Adams, H Ball, S Lawrenson, K Halim, S Russell, R Wells, C Strand, SH Ørntoft, TF Larson, M Armasu, S Massie, CE Asim, M Mortensen, MM Borre, M Woodfine, K Warren, AY Lamb, AD Kay, J Whitaker, H Ramos-Montoya, A Murrell, A Sørensen, KD Fridley, BL Goode, EL Gayther, SA Masters, J Neal, DE Mills, IG |
| author_sort | Ross-Adams, H |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:00:23Z |
| format | Journal article |
| id | oxford-uuid:b0c39d53-2c7d-4b4b-b70e-84d324b34814 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:00:23Z |
| publishDate | 2016 |
| publisher | Rapamycin Press |
| record_format | dspace |
| spelling | oxford-uuid:b0c39d53-2c7d-4b4b-b70e-84d324b348142022-03-27T03:58:54ZHNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b0c39d53-2c7d-4b4b-b70e-84d324b34814EnglishSymplectic Elements at OxfordRapamycin Press2016Ross-Adams, HBall, SLawrenson, KHalim, SRussell, RWells, CStrand, SHØrntoft, TFLarson, MArmasu, SMassie, CEAsim, MMortensen, MMBorre, MWoodfine, KWarren, AYLamb, ADKay, JWhitaker, HRamos-Montoya, AMurrell, ASørensen, KDFridley, BLGoode, ELGayther, SAMasters, JNeal, DEMills, IGTwo 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. |
| spellingShingle | Ross-Adams, H Ball, S Lawrenson, K Halim, S Russell, R Wells, C Strand, SH Ørntoft, TF Larson, M Armasu, S Massie, CE Asim, M Mortensen, MM Borre, M Woodfine, K Warren, AY Lamb, AD Kay, J Whitaker, H Ramos-Montoya, A Murrell, A Sørensen, KD Fridley, BL Goode, EL Gayther, SA Masters, J Neal, DE Mills, IG HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer |
| title | HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer |
| title_full | HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer |
| title_fullStr | HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer |
| title_full_unstemmed | HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer |
| title_short | HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer |
| title_sort | hnf1b variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer |
| work_keys_str_mv | AT rossadamsh hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT balls hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT lawrensonk hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT halims hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT russellr hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT wellsc hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT strandsh hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT ørntofttf hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT larsonm hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT armasus hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT massiece hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT asimm hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT mortensenmm hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT borrem hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT woodfinek hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT warrenay hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT lambad hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT kayj hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT whitakerh hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT ramosmontoyaa hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT murrella hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT sørensenkd hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT fridleybl hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT goodeel hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT gaythersa hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT mastersj hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT nealde hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer AT millsig hnf1bvariantsassociatewithpromotermethylationandregulategenenetworksactivatedinprostateandovariancancer |