TY  - JOUR
A1  - Enjuanes, Anna
A1  - Fernandez, Veronica
A1  - Hernandez, Luis
A1  - Navarro, Alba
A1  - Bea, Silvia
A1  - Pinyol, Magda
A1  - Lopez-Guillermo, Armando
A1  - Rosenwald, Andreas
A1  - Ott, German
A1  - Campo, Elias
A1  - Jares, Pedro
T1  - Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma
JF  - PLoS ONE
N2  - 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.
KW  - Histone deacetylase inhibition
KW  - Genome wide analysis
KW  - Molecular pathogenesis
KW  - DNA hypermethylation
KW  - Breast-cancer
KW  - Lung-cancer
KW  - Promoter
KW  - Expression
KW  - Targets
KW  - Sox9
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140632
VL  - 6
IS  - 5
ER  -