@article{6136b9c45d2e40c1bbaef84240ddd852,
title = "Further Confirmation of Germline Glioma Risk Variant rs78378222 in TP53 and Its Implication in Tumor Tissues via Integrative Analysis of TCGA Data",
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.",
keywords = "Glioma, Rare SNP, TCGA, TP53",
author = "Zhaoming Wang and Preetha Rajaraman and Melin, {Beatrice S.} and Chung, {Charles C.} and Weijia Zhang and Roberta Mckean-Cowdin and Dominique Michaud and Meredith Yeager and Anders Ahlbom and Demetrius Albanes and Ulrika Andersson and Freeman, {Laura E.Beane} and Buring, {Julie E.} and Butler, {Mary Ann} and Tania Carre{\'o}n and Maria Feychting and Gapstur, {Susan M.} and Gaziano, {J. Michael} and Giles, {Graham G.} and Goran Hallmans and Roger Henriksson and Judith Hoffman-Bolton and Inskip, {Peter D.} and Kitahara, {Cari M.} and Marchand, {Loic Le} and Linet, {Martha S.} and Shengchao Li and Ulrike Peters and Purdue, {Mark P.} and Nathaniel Rothman and Ruder, {Avima M.} and Sesso, {Howard D.} and Gianluca Severi and Meir Stampfer and Stevens, {Victoria L.} and Kala Visvanathan and Wang, {Sophia S.} and Emily White and Anne Zeleniuch-Jacquotte and Robert Hoover and Fraumeni, {Joseph F.} and Nilanjan Chatterjee and Patricia Hartge and Chanock, {Stephen J.}",
note = "Publisher Copyright: {\textcopyright} 2015 WILEY PERIODICALS, INC.",
year = "2015",
month = jul,
day = "1",
doi = "10.1002/humu.22799",
language = "English (US)",
volume = "36",
pages = "684--688",
journal = "Human mutation",
issn = "1059-7794",
publisher = "Wiley-Liss Inc.",
number = "7",
}