title: Identification of methylated genes associated with aggressive clinicopathological features in mantle cell lymphoma.
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.
  
  
  RESULTS
  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.
authors: Hematopathology Section, Department of Anatomic Pathology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors: Anna
authors: A
authors: Enjuanes
authors: Verònica
authors: V
authors: Fernàndez
authors: Luis
authors: L
authors: Hernández
authors: Alba
authors: A
authors: Navarro
authors: Sílvia
authors: S
authors: Beà
authors: Magda
authors: M
authors: Pinyol
authors: Armando
authors: A
authors: López-Guillermo
authors: Andreas
authors: A
authors: Rosenwald
authors: German
authors: G
authors: Ott
authors: Elías
authors: E
authors: Campo
authors: Pedro
authors: P
authors: Jares
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