Identification of methylated genes associated with aggressive clinicopathological features in mantle cell lymphoma.

<h4>Background</h4>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 sil...

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Autores principales:	Anna Enjuanes, Verònica Fernàndez, Luis Hernández, Alba Navarro, Sílvia Beà, Magda Pinyol, Armando López-Guillermo, Andreas Rosenwald, German Ott, Elías Campo, Pedro Jares
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/69e86e41d29b42ba9e4a8e9ac3fe8e43
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spelling	oai:doaj.org-article:69e86e41d29b42ba9e4a8e9ac3fe8e432021-11-18T06:53:56ZIdentification of methylated genes associated with aggressive clinicopathological features in mantle cell lymphoma.1932-620310.1371/journal.pone.0019736https://doaj.org/article/69e86e41d29b42ba9e4a8e9ac3fe8e432011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21603610/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.Anna EnjuanesVerònica FernàndezLuis HernándezAlba NavarroSílvia BeàMagda PinyolArmando López-GuillermoAndreas RosenwaldGerman OttElías CampoPedro JaresPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e19736 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Enjuanes Verònica Fernàndez Luis Hernández Alba Navarro Sílvia Beà Magda Pinyol Armando López-Guillermo Andreas Rosenwald German Ott Elías Campo Pedro Jares Identification of methylated genes associated with aggressive clinicopathological features in mantle cell lymphoma.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.
format	article
author	Anna Enjuanes Verònica Fernàndez Luis Hernández Alba Navarro Sílvia Beà Magda Pinyol Armando López-Guillermo Andreas Rosenwald German Ott Elías Campo Pedro Jares
author_facet	Anna Enjuanes Verònica Fernàndez Luis Hernández Alba Navarro Sílvia Beà Magda Pinyol Armando López-Guillermo Andreas Rosenwald German Ott Elías Campo Pedro Jares
author_sort	Anna Enjuanes
title	Identification of methylated genes associated with aggressive clinicopathological features in mantle cell lymphoma.
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.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/69e86e41d29b42ba9e4a8e9ac3fe8e43
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Identification of methylated genes associated with aggressive clinicopathological features in mantle cell lymphoma.

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