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Title: Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma
Author: 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
Keywords: Cicle cel·lular
Genètica molecular
Cell cycle
Molecular genetics
Issue Date: 16-May-2011
Publisher: Public Library of Science (PLoS)
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: PLoS One, 2011, vol. 6, num. 5, p. e19736
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Fonaments Clínics)

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