| Literature DB >> 25907361 |
Zhaoming Wang1,2, Preetha Rajaraman1, Beatrice S Melin3, Charles C Chung1,2, Weijia Zhang4, Roberta McKean-Cowdin5, Dominique Michaud6,7, Meredith Yeager1,2, Anders Ahlbom8, Demetrius Albanes1, Ulrika Andersson3, Laura E Beane Freeman1, Julie E Buring9, Mary Ann Butler10, Tania Carreón10, Maria Feychting8, Susan M Gapstur11, J Michael Gaziano9,12, Graham G Giles13,14, Goran Hallmans15, Roger Henriksson3, Judith Hoffman-Bolton16, Peter D Inskip1, Cari M Kitahara1, Loic Le Marchand17, Martha S Linet1, Shengchao Li1,2, Ulrike Peters18,19, Mark P Purdue1, Nathaniel Rothman1, Avima M Ruder10, Howard D Sesso9, Gianluca Severi13,14, Meir Stampfer20,21, Victoria L Stevens11, Kala Visvanathan16,22, Sophia S Wang23, Emily White18,19, Anne Zeleniuch-Jacquotte24, Robert Hoover1, Joseph F Fraumeni1, Nilanjan Chatterjee1, Patricia Hartge1, Stephen J Chanock1.
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 haplotype carrying common protective allele (A) occurred somatically in GBM but not in LUAD. Our bioinformatic analysis suggests rare risk allele (C) disrupts mRNA termination, and an allelic loss of a genomic region harboring common protective allele (A) occurs during tumor initiation or progression for glioma.Entities:
Keywords: TCGA; TP53; glioma; rare SNP
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Year: 2015 PMID： 25907361 PMCID： PMC4750473 DOI： 10.1002/humu.22799
Source DB: PubMed Journal: Hum Mutat ISSN： 1059-7794 Impact factor: 4.878