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 Carreón; Maria Feychting; Susan M. Gapstur; J. Michael Gaziano; Graham G. Giles; Goran Hallmans; Roger Henriksson; Judith Hoffman-Bolton; Peter D. Inskip; Cari M. Kitahara; Loic Le Marchand; Martha S. Linet; Shengchao Li; Ulrike Peters; Mark P. Purdue; Nathaniel Rothman; Avima M. Ruder; Howard D. Sesso; Gianluca Severi; Meir Stampfer; Victoria L. Stevens; Kala Visvanathan; Sophia S. Wang; Emily White; Anne Zeleniuch-Jacquotte; Robert Hoover; Joseph F. Fraumeni; Nilanjan Chatterjee; Patricia Hartge; Stephen J. Chanock

doi:10.1002/humu.22799

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 Carreón, Maria Feychting, Susan M. Gapstur, J. Michael Gaziano, Graham G. Giles, Goran HallmansRoger Henriksson, Judith Hoffman-Bolton, Peter D. Inskip, Cari M. Kitahara, Loic Le Marchand, Martha S. Linet, Shengchao Li, Ulrike Peters, Mark P. Purdue, Nathaniel Rothman, Avima M. Ruder, Howard D. Sesso, Gianluca Severi, Meir Stampfer, Victoria L. Stevens, Kala Visvanathan, Sophia S. Wang, Emily White, Anne Zeleniuch-Jacquotte, Robert Hoover, Joseph F. Fraumeni, Nilanjan Chatterjee, Patricia Hartge, Stephen J. Chanock

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

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.

Original language	English
Pages (from-to)	684-688
Number of pages	5
Journal	Human Mutation
Volume	36
Issue number	7
DOIs	https://doi.org/10.1002/humu.22799
Publication status	Published - 1 Jul 2015
Externally published	Yes

Keywords

Glioma
Rare SNP
TCGA
TP53

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Wang, Z., Rajaraman, P., Melin, B. S., Chung, C. C., Zhang, W., Mckean-Cowdin, R., Michaud, D., Yeager, M., Ahlbom, A., Albanes, D., Andersson, U., Freeman, L. E. B., Buring, J. E., Butler, M. A., Carreón, T., Feychting, M., Gapstur, S. M., Gaziano, J. M., Giles, G. G., ... Chanock, S. J. (2015). Further Confirmation of Germline Glioma Risk Variant rs78378222 in TP53 and Its Implication in Tumor Tissues via Integrative Analysis of TCGA Data. Human Mutation, 36(7), 684-688. https://doi.org/10.1002/humu.22799

@article{38d053dd235041aa87190dd43daf6f22,

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",

volume = "36",

pages = "684--688",

journal = "Human Mutation",

issn = "1059-7794",

number = "7",

}

Wang, Z, Rajaraman, P, Melin, BS, Chung, CC, Zhang, W, Mckean-Cowdin, R, Michaud, D, Yeager, M, Ahlbom, A, Albanes, D, Andersson, U, Freeman, LEB, Buring, JE, Butler, MA, Carreón, T, Feychting, M, Gapstur, SM, Gaziano, JM, Giles, GG, Hallmans, G, Henriksson, R, Hoffman-Bolton, J, Inskip, PD, Kitahara, CM, Marchand, LL, Linet, MS, Li, S, Peters, U, Purdue, MP, Rothman, N, Ruder, AM, Sesso, HD, Severi, G, Stampfer, M, Stevens, VL, Visvanathan, K, Wang, SS, White, E, Zeleniuch-Jacquotte, A, Hoover, R, Fraumeni, JF, Chatterjee, N, Hartge, P & Chanock, SJ 2015, 'Further Confirmation of Germline Glioma Risk Variant rs78378222 in TP53 and Its Implication in Tumor Tissues via Integrative Analysis of TCGA Data', Human Mutation, vol. 36, no. 7, pp. 684-688. https://doi.org/10.1002/humu.22799

TY - JOUR

T1 - Further Confirmation of Germline Glioma Risk Variant rs78378222 in TP53 and Its Implication in Tumor Tissues via Integrative Analysis of TCGA Data

AU - Wang, Zhaoming

AU - Rajaraman, Preetha

AU - Melin, Beatrice S.

AU - Chung, Charles C.

AU - Zhang, Weijia

AU - Mckean-Cowdin, Roberta

AU - Michaud, Dominique

AU - Yeager, Meredith

AU - Ahlbom, Anders

AU - Albanes, Demetrius

AU - Andersson, Ulrika

AU - Freeman, Laura E.Beane

AU - Buring, Julie E.

AU - Butler, Mary Ann

AU - Carreón, Tania

AU - Feychting, Maria

AU - Gapstur, Susan M.

AU - Gaziano, J. Michael

AU - Giles, Graham G.

AU - Hallmans, Goran

AU - Henriksson, Roger

AU - Hoffman-Bolton, Judith

AU - Inskip, Peter D.

AU - Kitahara, Cari M.

AU - Marchand, Loic Le

AU - Linet, Martha S.

AU - Li, Shengchao

AU - Peters, Ulrike

AU - Purdue, Mark P.

AU - Rothman, Nathaniel

AU - Ruder, Avima M.

AU - Sesso, Howard D.

AU - Severi, Gianluca

AU - Stampfer, Meir

AU - Stevens, Victoria L.

AU - Visvanathan, Kala

AU - Wang, Sophia S.

AU - White, Emily

AU - Zeleniuch-Jacquotte, Anne

AU - Hoover, Robert

AU - Fraumeni, Joseph F.

AU - Chatterjee, Nilanjan

AU - Hartge, Patricia

AU - Chanock, Stephen J.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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.

AB - 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.

KW - Glioma

KW - Rare SNP

KW - TCGA

KW - TP53

UR - http://www.scopus.com/inward/record.url?scp=84931577278&partnerID=8YFLogxK

U2 - 10.1002/humu.22799

DO - 10.1002/humu.22799

M3 - Article

C2 - 25907361

AN - SCOPUS:84931577278

SN - 1059-7794

VL - 36

SP - 684

EP - 688

JO - Human Mutation

JF - Human Mutation

IS - 7

ER -

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

Abstract

Keywords

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