Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma

Background: Mantle cell lymphoma (MCL) is genetically characterized by the t(11;14)(q13;q32) translocation and a high number of secondary chromosomal alterations. The contribution of DNA methylation to MCL lymphomagenesis is not well known. We sought to identify epigenetically silenced genes in thes...

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Autores: Enjuanes, Anna, Fernàndez Pascual, Verònica, Hernández, Luis, Navarro, Alba, Beà Bobet, Sílvia M., Pinyol, Magda, López Guillermo, Armando, Rosenwald, Andreas, Ott, German, Campo Güerri, Elias, Jares Gerboles, Pedro
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/43815
Acceso en línea:https://hdl.handle.net/2445/43815
Access Level:acceso abierto
Palabra clave:Cicle cel·lular
Limfomes
Genètica molecular
Carcinogènesi
Cell cycle
Lymphomas
Molecular genetics
Carcinogenesis
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spelling Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell LymphomaEnjuanes, AnnaFernàndez Pascual, VerònicaHernández, LuisNavarro, AlbaBeà Bobet, Sílvia M.Pinyol, MagdaLópez Guillermo, ArmandoRosenwald, AndreasOtt, GermanCampo Güerri, EliasJares Gerboles, PedroCicle cel·lularLimfomesGenètica molecularCarcinogènesiCell cycleLymphomasMolecular geneticsCarcinogenesisBackground: Mantle cell lymphoma (MCL) is genetically characterized by the t(11;14)(q13;q32) translocation and a high number of secondary chromosomal alterations. The contribution of DNA methylation to MCL lymphomagenesis is not well known. We sought to identify epigenetically silenced genes in these tumours that might have clinical relevance. Methodology/Principal Findings: To identify potential methylated genes in MCL we initially investigated seven MCL cell lines treated with epigenetic drugs and gene expression microarray profiling. The methylation status of selected candidate genes was validated by a quantitative assay and subsequently analyzed in a series of primary MCL (n=38). After pharmacological reversion we identified 252 potentially methylated genes. The methylation analysis of a subset of these genes (n=25) in the MCL cell lines and normal B lymphocytes confirmed that 80% of them were methylated in the cell lines but not in normal lymphocytes. The subsequent analysis in primary MCL identified five genes (SOX9,HOXA9,AHR,NR2F2 ,and ROBO1) frequently methylated in these tumours. The gene methylation events tended to occur in the same primary neoplasms and correlated with higher proliferation, increased number of chromosomal abnormalities, and shorter survival of the patients. Conclusions: We have identified a set of genes whose methylation degree and gene expression levels correlate with aggressive clinicopathological features of MCL. Our findings also suggest that a subset of MCL might show a CpG island methylator phenotype (CIMP) that may influence the behaviour of the tumours.Public Library of Science (PLoS)2011info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/43815Articles publicats en revistes (Fonaments Clínics)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0019736PLoS One, 2011, vol. 6, num. 5, p. e19736http://dx.doi.org/10.1371/journal.pone.0019736cc-by (c) Enjuanes, A. et al., 2011http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/438152026-05-27T06:46:51Z
dc.title.none.fl_str_mv Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma
title Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma
spellingShingle Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma
Enjuanes, Anna
Cicle cel·lular
Limfomes
Genètica molecular
Carcinogènesi
Cell cycle
Lymphomas
Molecular genetics
Carcinogenesis
title_short Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma
title_full Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma
title_fullStr Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma
title_full_unstemmed Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma
title_sort Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma
dc.creator.none.fl_str_mv Enjuanes, Anna
Fernàndez Pascual, Verònica
Hernández, Luis
Navarro, Alba
Beà Bobet, Sílvia M.
Pinyol, Magda
López Guillermo, Armando
Rosenwald, Andreas
Ott, German
Campo Güerri, Elias
Jares Gerboles, Pedro
author Enjuanes, Anna
author_facet Enjuanes, Anna
Fernàndez Pascual, Verònica
Hernández, Luis
Navarro, Alba
Beà Bobet, Sílvia M.
Pinyol, Magda
López Guillermo, Armando
Rosenwald, Andreas
Ott, German
Campo Güerri, Elias
Jares Gerboles, Pedro
author_role author
author2 Fernàndez Pascual, Verònica
Hernández, Luis
Navarro, Alba
Beà Bobet, Sílvia M.
Pinyol, Magda
López Guillermo, Armando
Rosenwald, Andreas
Ott, German
Campo Güerri, Elias
Jares Gerboles, Pedro
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cicle cel·lular
Limfomes
Genètica molecular
Carcinogènesi
Cell cycle
Lymphomas
Molecular genetics
Carcinogenesis
topic Cicle cel·lular
Limfomes
Genètica molecular
Carcinogènesi
Cell cycle
Lymphomas
Molecular genetics
Carcinogenesis
description Background: Mantle cell lymphoma (MCL) is genetically characterized by the t(11;14)(q13;q32) translocation and a high number of secondary chromosomal alterations. The contribution of DNA methylation to MCL lymphomagenesis is not well known. We sought to identify epigenetically silenced genes in these tumours that might have clinical relevance. Methodology/Principal Findings: To identify potential methylated genes in MCL we initially investigated seven MCL cell lines treated with epigenetic drugs and gene expression microarray profiling. The methylation status of selected candidate genes was validated by a quantitative assay and subsequently analyzed in a series of primary MCL (n=38). After pharmacological reversion we identified 252 potentially methylated genes. The methylation analysis of a subset of these genes (n=25) in the MCL cell lines and normal B lymphocytes confirmed that 80% of them were methylated in the cell lines but not in normal lymphocytes. The subsequent analysis in primary MCL identified five genes (SOX9,HOXA9,AHR,NR2F2 ,and ROBO1) frequently methylated in these tumours. The gene methylation events tended to occur in the same primary neoplasms and correlated with higher proliferation, increased number of chromosomal abnormalities, and shorter survival of the patients. Conclusions: We have identified a set of genes whose methylation degree and gene expression levels correlate with aggressive clinicopathological features of MCL. Our findings also suggest that a subset of MCL might show a CpG island methylator phenotype (CIMP) that may influence the behaviour of the tumours.
publishDate 2011
dc.date.none.fl_str_mv 2011
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/2445/43815
url https://hdl.handle.net/2445/43815
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0019736
PLoS One, 2011, vol. 6, num. 5, p. e19736
http://dx.doi.org/10.1371/journal.pone.0019736
dc.rights.none.fl_str_mv cc-by (c) Enjuanes, A. et al., 2011
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Enjuanes, A. et al., 2011
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 (Fonaments Clínics)
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 15,300719

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