{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yanchus C"],"funding":["Cancer Research UK","NHGRI NIH HHS","NCI NIH HHS","NINDS NIH HHS","NIGMS NIH HHS"],"pagination":["68-78"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9926876"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["378(6615)"],"pubmed_abstract":["Establishing causal links between inherited polymorphisms and cancer risk is challenging. Here, we focus on the single-nucleotide polymorphism rs55705857, which confers a sixfold greater risk of isocitrate dehydrogenase (<i>IDH)</i>-mutant low-grade glioma (LGG). We reveal that rs55705857 itself is the causal variant and is associated with molecular pathways that drive LGG. Mechanistically, we show that rs55705857 resides within a brain-specific enhancer, where the risk allele disrupts OCT2/4 binding, allowing increased interaction with the <i>Myc</i> promoter and increased <i>Myc</i> expression. Mutating the orthologous mouse rs55705857 locus accelerated tumor development in an <i>Idh1</i><sup>R132H</sup>-driven LGG mouse model from 472 to 172 days and increased penetrance from 30% to 75%"],"journal":["Science (New York, N.Y.)"],"pubmed_title":["A noncoding single-nucleotide polymorphism at 8q24 drives &lt;i&gt;IDH1&lt;/i&gt;-mutant glioma formation."],"pmcid":["PMC9926876"],"funding_grant_id":["P50 CA097257","P50 CA108961","T32 NS082174","R01 CA207360","R01 CA052689","DP2 GM149555","U24 CA220242","R01 HG003988","R01 CA139020","27603","R01 CA230712","R00 HG009682","P30 CA015083","R01 CA119215"],"pubmed_authors":["Visel A","Dickel DE","Yanchus C","Gosio JT","Schramek D","Kollmeyer TM","Ahmed M","Wang L","Winick-Ng W","Malik A","Liang M","Tsai R","Taylor MD","Zadeh G","Dennis JW","Pawling J","Maass PG","Drucker KL","Mazrooei P","Wrana J","Murphy DJ","Hollingsworth EW","Carson B","Mak T","Jiang L","Michealraj KA","Trcka D","He HH","Lachance DH","Dirks P","Pennacchio LA","De Lorenzo SB","Lupien M","Lowden C","Geuenich M","Al-Zahrani KN","Hernandez JJ","Loganathan SK","Wilson MD","Pombo A","Ali A","Jenkins RB","Abyzov A","Browning JWL","Wiencke J","Zhou L","Elia A","Kosel ML","Attisano L","Jacinto S","Berman J","Panda A","Eckel-Passow JE","Campbell K","Wrensch M","Kvon EZ","Fortin J","Ida CM","Decker PA"],"additional_accession":[]},"is_claimable":false,"name":"A noncoding single-nucleotide polymorphism at 8q24 drives &lt;i&gt;IDH1&lt;/i&gt;-mutant glioma formation.","description":"Establishing causal links between inherited polymorphisms and cancer risk is challenging. Here, we focus on the single-nucleotide polymorphism rs55705857, which confers a sixfold greater risk of isocitrate dehydrogenase (<i>IDH)</i>-mutant low-grade glioma (LGG). We reveal that rs55705857 itself is the causal variant and is associated with molecular pathways that drive LGG. Mechanistically, we show that rs55705857 resides within a brain-specific enhancer, where the risk allele disrupts OCT2/4 binding, allowing increased interaction with the <i>Myc</i> promoter and increased <i>Myc</i> expression. Mutating the orthologous mouse rs55705857 locus accelerated tumor development in an <i>Idh1</i><sup>R132H</sup>-driven LGG mouse model from 472 to 172 days and increased penetrance from 30% to 75%","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2025-08-13T03:04:25.592Z","creation":"2025-02-19T03:27:05.849Z"},"accession":"S-EPMC9926876","cross_references":{"pubmed":["36201590"],"doi":["10.1126/science.abj2890"]}}