Details

Autor(en) / Beteiligte

• Ross-Adams, Helen
• Ball, Stephen
• Lawrenson, Kate
• Halim, Silvia
• Russell, Roslin
• Wells, Claire
• Strand, Siri H
• Ørntoft, Torben F
• Larson, Melissa
• Armasu, Sebastian
• Massie, Charles E
• Asim, Mohammad
• Mortensen, Martin M
• Borre, Michael
• Woodfine, Kathryn
• Warren, Anne Y
• Lamb, Alastair D
• Kay, Jonathan
• Whitaker, Hayley
• Ramos-Montoya, Antonio
• Murrell, Adele
• Sørensen, Karina D
• Fridley, Brooke L
• Goode, Ellen L
• Gayther, Simon A
• Masters, John
• Neal, David E
• Mills, Ian G

Titel

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

Ist Teil von

• Oncotarget, 2016-11, Vol.7 (46), p.74734-74746

Ort / Verlag

United States: Impact Journals LLC

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.