Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression.
Although genome-wide association studies (GWAS) have identified the existence of numerous population-based cancer susceptibility loci, mechanistic insights remain limited, particularly for intergenic polymorphisms. Here, we show that polymorphism at a remote intergenic region on chromosome 11q13.3,...
| Hauptverfasser: | , , , , , , , , |
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| Format: | Journal article |
| Sprache: | English |
| Veröffentlicht: |
2012
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| _version_ | 1826284200950497280 |
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| author | Schödel, J Bardella, C Sciesielski, L Brown, J Pugh, C Buckle, V Tomlinson, I Ratcliffe, P Mole, DR |
| author_facet | Schödel, J Bardella, C Sciesielski, L Brown, J Pugh, C Buckle, V Tomlinson, I Ratcliffe, P Mole, DR |
| author_sort | Schödel, J |
| collection | OXFORD |
| description | Although genome-wide association studies (GWAS) have identified the existence of numerous population-based cancer susceptibility loci, mechanistic insights remain limited, particularly for intergenic polymorphisms. Here, we show that polymorphism at a remote intergenic region on chromosome 11q13.3, recently identified as a susceptibility locus for renal cell carcinoma, modulates the binding and function of hypoxia-inducible factor (HIF) at a previously unrecognized transcriptional enhancer of CCND1 (encoding cyclin D1) that is specific for renal cancers characterized by inactivation of the von Hippel-Lindau tumor suppressor (pVHL). The protective haplotype impairs binding of HIF-2, resulting in an allelic imbalance in cyclin D1 expression, thus affecting a link between hypoxia pathways and cell cycle control. |
| first_indexed | 2024-03-07T01:10:19Z |
| format | Journal article |
| id | oxford-uuid:8cc6ceea-f214-4d03-a7e6-a9ca25d0a3dc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:10:19Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:8cc6ceea-f214-4d03-a7e6-a9ca25d0a3dc2022-03-26T22:46:43ZCommon genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8cc6ceea-f214-4d03-a7e6-a9ca25d0a3dcEnglishSymplectic Elements at Oxford2012Schödel, JBardella, CSciesielski, LBrown, JPugh, CBuckle, VTomlinson, IRatcliffe, PMole, DRAlthough genome-wide association studies (GWAS) have identified the existence of numerous population-based cancer susceptibility loci, mechanistic insights remain limited, particularly for intergenic polymorphisms. Here, we show that polymorphism at a remote intergenic region on chromosome 11q13.3, recently identified as a susceptibility locus for renal cell carcinoma, modulates the binding and function of hypoxia-inducible factor (HIF) at a previously unrecognized transcriptional enhancer of CCND1 (encoding cyclin D1) that is specific for renal cancers characterized by inactivation of the von Hippel-Lindau tumor suppressor (pVHL). The protective haplotype impairs binding of HIF-2, resulting in an allelic imbalance in cyclin D1 expression, thus affecting a link between hypoxia pathways and cell cycle control. |
| spellingShingle | Schödel, J Bardella, C Sciesielski, L Brown, J Pugh, C Buckle, V Tomlinson, I Ratcliffe, P Mole, DR Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression. |
| title | Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression. |
| title_full | Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression. |
| title_fullStr | Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression. |
| title_full_unstemmed | Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression. |
| title_short | Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression. |
| title_sort | common genetic variants at the 11q13 3 renal cancer susceptibility locus influence binding of hif to an enhancer of cyclin d1 expression |
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