Journal article

Further Confirmation of Germline Glioma Risk Variant rs78378222 in TP53 and Its Implication in Tumor Tissues via Integrative Analysis of TCGA Data

Zhaoming Wang, Preetha Rajaraman, Beatrice S Melin, Charles C Chung, Weijia Zhang, Roberta McKean-Cowdin, Dominique Michaud, Meredith Yeager, Anders Ahlbom, Demetrius Albanes, Ulrika Andersson, Laura E Beane Freeman, Julie E Buring, Mary Ann Butler, Tania Carreon, Maria Feychting, Susan M Gapstur, J Michael Gaziano, Graham G Giles, Goran Hallmans Show all

Human Mutation | WILEY | Published : 2015

Abstract

We confirmed strong association of rs78378222:A>C (per allele odds ratio [OR] = 3.14; P = 6.48 × 10(-11) ), a germline rare single-nucleotide polymorphism (SNP) in TP53, via imputation of a genome-wide association study of glioma (1,856 cases and 4,955 controls). We subsequently performed integrative analyses on the Cancer Genome Atlas (TCGA) data for GBM (glioblastoma multiforme) and LUAD (lung adenocarcinoma). Based on SNP data, we imputed genotypes for rs78378222 and selected individuals carrying rare risk allele (C). Using RNA sequencing data, we observed aberrant transcripts with ∼3 kb longer than normal for those individuals. Using exome sequencing data, we further showed that loss of ..

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