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题目:: Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression.
作者:: Schödel(Johannes),Bardella(Chiara),Sciesielski(Lina K),Brown(Jill M),Pugh(Chris W),Buckle(Veronica),Tomlinson(Ian P),Ratcliffe(Peter J),Mole(David R)
状态:: 发布时间2012-03-29 , 更新时间 2016-11-25
期刊:: Nat Genet
摘要:: 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.
语言:: eng
DOI:

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