Multiple renal cancer susceptibility polymorphisms modulate the HIF pathway
Publication Date
July 17, 2017
Authors
Steffen Grampp, Virginia Schmid, Rafik Salama, Victoria Lauer, et al
Volume
13
Issue
7
Pages
e1006872
DOI
https://dx.plos.org/10.1371/journal.pgen.1006872
Publisher URL
http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1006872
Scopus
85026651387
Mendeley
http://www.mendeley.com/research/multiple-renal-cancer-susceptibility-polymorphisms-modulate-hif-pathway
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Mendeley | Further Information

{"title"=>"Multiple renal cancer susceptibility polymorphisms modulate the HIF pathway", "type"=>"journal", "authors"=>[{"first_name"=>"Steffen", "last_name"=>"Grampp", "scopus_author_id"=>"56048775200"}, {"first_name"=>"Virginia", "last_name"=>"Schmid", "scopus_author_id"=>"57195266467"}, {"first_name"=>"Rafik", "last_name"=>"Salama", "scopus_author_id"=>"56888517500"}, {"first_name"=>"Victoria", "last_name"=>"Lauer", "scopus_author_id"=>"57190795568"}, {"first_name"=>"Franziska", "last_name"=>"Kranz", "scopus_author_id"=>"57191647041"}, {"first_name"=>"James L.", "last_name"=>"Platt", "scopus_author_id"=>"55676828500"}, {"first_name"=>"James", "last_name"=>"Smythies", "scopus_author_id"=>"56428726200"}, {"first_name"=>"Hani", "last_name"=>"Choudhry", "scopus_author_id"=>"37004303400"}, {"first_name"=>"Margarete", "last_name"=>"Goppelt-Struebe", "scopus_author_id"=>"7006211474"}, {"first_name"=>"Peter J.", "last_name"=>"Ratcliffe", "scopus_author_id"=>"35273349500"}, {"first_name"=>"David R.", "last_name"=>"Mole", "scopus_author_id"=>"7006082609"}, {"first_name"=>"Johannes", "last_name"=>"Schödel", "scopus_author_id"=>"14039591600"}], "year"=>2017, "source"=>"PLoS Genetics", "identifiers"=>{"scopus"=>"2-s2.0-85026651387", "sgr"=>"85026651387", "doi"=>"10.1371/journal.pgen.1006872", "pui"=>"617639003", "pmid"=>"28715484", "isbn"=>"1111111111", "issn"=>"15537404"}, "id"=>"a1e1426e-36ee-3bef-9678-e118d8308416", "abstract"=>"© 2017 Grampp et al. Un-physiological activation of hypoxia inducible factor (HIF) is an early event in most renal cell cancers (RCC) following inactivation of the von Hippel-Lindau tumor suppressor. Despite intense study, how this impinges on cancer development is incompletely understood. To test for the impact of genetic signals on this pathway, we aligned human RCC-susceptibility polymorphisms with genome-wide assays of HIF-binding and observed highly significant overlap. Allele-specific assays of HIF binding, chromatin conformation and gene expression together with eQTL analyses in human tumors were applied to mechanistic analysis of one such overlapping site at chromosome 12p12.1. This defined a novel stage-specific mechanism in which the risk polymorphism, rs12814794, directly creates a new HIF-binding site that mediates HIF-1α isoform specific upregulation of its target BHLHE41. The alignment of multiple sites in the HIF cis-acting apparatus with RCC-susceptibility polymorphisms strongly supports a causal model in which minor variation in this pathway exerts significant effects on RCC development.", "link"=>"http://www.mendeley.com/research/multiple-renal-cancer-susceptibility-polymorphisms-modulate-hif-pathway", "reader_count"=>11, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>1, "Professor"=>1, "Unspecified"=>5}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>1, "Professor"=>1, "Unspecified"=>5}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>1, "Computer Science"=>1, "Unspecified"=>5}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>5}}, "group_count"=>2}

Scopus | Further Information

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