Exploring the Link Between Germline and Somatic Genetic Alterations in Breast Carcinogenesis

Recent genome-wide association studies (GWASs) have identified candidate genes contributing to cancer risk through low-penetrance mutations. Many of these genes were unexpected and, intriguingly, included well-known players in carcinogenesis at the somatic level. To assess the hypothesis of a germli...

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Autores: Bonifaci Cano, Núria, Gorski, Bohdan, Masojć, Bartlomiej, Wokolorczyk, Dominika, Jakubowska, Anna, Dębniak, Tadeusz, Berenguer, Antoni, Serra-Musach, Jordi, Brunet, Joan, Dopazo, Joaquín, Narod, Steven A., Lubinski, Jan, Lázaro García, Conxi, Cybulski, Cezary, Pujana Genestar, M. Ángel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/126789
Acceso en línea:https://hdl.handle.net/2445/126789
Access Level:acceso abierto
Palabra clave:Càncer de mama
Carcinogènesi
Breast cancer
Carcinogenesis
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spelling Exploring the Link Between Germline and Somatic Genetic Alterations in Breast CarcinogenesisBonifaci Cano, NúriaGorski, BohdanMasojć, BartlomiejWokolorczyk, DominikaJakubowska, AnnaDębniak, TadeuszBerenguer, AntoniSerra-Musach, JordiBrunet, JoanDopazo, JoaquínNarod, Steven A.Lubinski, JanLázaro García, ConxiCybulski, CezaryPujana Genestar, M. ÁngelCàncer de mamaCarcinogènesiBreast cancerCarcinogenesisRecent genome-wide association studies (GWASs) have identified candidate genes contributing to cancer risk through low-penetrance mutations. Many of these genes were unexpected and, intriguingly, included well-known players in carcinogenesis at the somatic level. To assess the hypothesis of a germline-somatic link in carcinogenesis, we evaluated the distribution of somatic gene labels within the ordered results of a breast cancer risk GWAS. This analysis suggested frequent influence on risk of genetic variation in loci encoding for "driver kinases" (i.e., kinases encoded by genes that showed higher somatic mutation rates than expected by chance and, therefore, whose deregulation may contribute to cancer development and/or progression). Assessment of these predictions using a population-based case-control study in Poland replicated the association for rs3732568 in EPHB1 (odds ratio (OR) = 0.79; 95% confidence interval (CI): 0.63-0.98; P-trend = 0.031). Analyses by early age at diagnosis and by estrogen receptor alpha (ER alpha) tumor status indicated potential associations for rs6852678 in CDKL2 (OR = 0.32, 95% CI: 0.10-1.00; P-recessive = 0.044) and rs10878640 in DYRK2 (OR = 2.39, 95% CI: 1.32-4.30; P-dominant = 0.003), and for rs12765929, rs9836340, rs4707795 in BMPR1A, EPHA3 and EPHA7, respectively (ER alpha tumor status P-interaction<0.05). The identification of three novel candidates as EPH receptor genes might indicate a link between perturbed compartmentalization of early neoplastic lesions and breast cancer risk and progression. Together, these data may lay the foundations for replication in additional populations and could potentially increase our knowledge of the underlying molecular mechanisms of breast carcinogenesis.Public Library of Science (PLoS)2010info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/126789Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1371/journal.pone.0014078PLoS One, 2010, vol. 5, num. 11, p. e14078https://doi.org/10.1371/journal.pone.0014078cc by (c) Bonifaci et al., 2010http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1267892026-05-27T06:46:51Z
dc.title.none.fl_str_mv Exploring the Link Between Germline and Somatic Genetic Alterations in Breast Carcinogenesis
title Exploring the Link Between Germline and Somatic Genetic Alterations in Breast Carcinogenesis
spellingShingle Exploring the Link Between Germline and Somatic Genetic Alterations in Breast Carcinogenesis
Bonifaci Cano, Núria
Càncer de mama
Carcinogènesi
Breast cancer
Carcinogenesis
title_short Exploring the Link Between Germline and Somatic Genetic Alterations in Breast Carcinogenesis
title_full Exploring the Link Between Germline and Somatic Genetic Alterations in Breast Carcinogenesis
title_fullStr Exploring the Link Between Germline and Somatic Genetic Alterations in Breast Carcinogenesis
title_full_unstemmed Exploring the Link Between Germline and Somatic Genetic Alterations in Breast Carcinogenesis
title_sort Exploring the Link Between Germline and Somatic Genetic Alterations in Breast Carcinogenesis
dc.creator.none.fl_str_mv Bonifaci Cano, Núria
Gorski, Bohdan
Masojć, Bartlomiej
Wokolorczyk, Dominika
Jakubowska, Anna
Dębniak, Tadeusz
Berenguer, Antoni
Serra-Musach, Jordi
Brunet, Joan
Dopazo, Joaquín
Narod, Steven A.
Lubinski, Jan
Lázaro García, Conxi
Cybulski, Cezary
Pujana Genestar, M. Ángel
author Bonifaci Cano, Núria
author_facet Bonifaci Cano, Núria
Gorski, Bohdan
Masojć, Bartlomiej
Wokolorczyk, Dominika
Jakubowska, Anna
Dębniak, Tadeusz
Berenguer, Antoni
Serra-Musach, Jordi
Brunet, Joan
Dopazo, Joaquín
Narod, Steven A.
Lubinski, Jan
Lázaro García, Conxi
Cybulski, Cezary
Pujana Genestar, M. Ángel
author_role author
author2 Gorski, Bohdan
Masojć, Bartlomiej
Wokolorczyk, Dominika
Jakubowska, Anna
Dębniak, Tadeusz
Berenguer, Antoni
Serra-Musach, Jordi
Brunet, Joan
Dopazo, Joaquín
Narod, Steven A.
Lubinski, Jan
Lázaro García, Conxi
Cybulski, Cezary
Pujana Genestar, M. Ángel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de mama
Carcinogènesi
Breast cancer
Carcinogenesis
topic Càncer de mama
Carcinogènesi
Breast cancer
Carcinogenesis
description Recent genome-wide association studies (GWASs) have identified candidate genes contributing to cancer risk through low-penetrance mutations. Many of these genes were unexpected and, intriguingly, included well-known players in carcinogenesis at the somatic level. To assess the hypothesis of a germline-somatic link in carcinogenesis, we evaluated the distribution of somatic gene labels within the ordered results of a breast cancer risk GWAS. This analysis suggested frequent influence on risk of genetic variation in loci encoding for "driver kinases" (i.e., kinases encoded by genes that showed higher somatic mutation rates than expected by chance and, therefore, whose deregulation may contribute to cancer development and/or progression). Assessment of these predictions using a population-based case-control study in Poland replicated the association for rs3732568 in EPHB1 (odds ratio (OR) = 0.79; 95% confidence interval (CI): 0.63-0.98; P-trend = 0.031). Analyses by early age at diagnosis and by estrogen receptor alpha (ER alpha) tumor status indicated potential associations for rs6852678 in CDKL2 (OR = 0.32, 95% CI: 0.10-1.00; P-recessive = 0.044) and rs10878640 in DYRK2 (OR = 2.39, 95% CI: 1.32-4.30; P-dominant = 0.003), and for rs12765929, rs9836340, rs4707795 in BMPR1A, EPHA3 and EPHA7, respectively (ER alpha tumor status P-interaction<0.05). The identification of three novel candidates as EPH receptor genes might indicate a link between perturbed compartmentalization of early neoplastic lesions and breast cancer risk and progression. Together, these data may lay the foundations for replication in additional populations and could potentially increase our knowledge of the underlying molecular mechanisms of breast carcinogenesis.
publishDate 2010
dc.date.none.fl_str_mv 2010
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/126789
url https://hdl.handle.net/2445/126789
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0014078
PLoS One, 2010, vol. 5, num. 11, p. e14078
https://doi.org/10.1371/journal.pone.0014078
dc.rights.none.fl_str_mv cc by (c) Bonifaci et al., 2010
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Bonifaci et al., 2010
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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