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To clarify the potential contribution of altered DNA methylation in the development and\/or progression of MCL, we performed genome\u2010wide methylation profiling of a large cohort of primary MCL tumors (<jats:italic>n<\/jats:italic> = 132), MCL cell lines (<jats:italic>n<\/jats:italic> = 6) and normal lymphoid tissue samples (<jats:italic>n<\/jats:italic> = 31), using the Infinium HumanMethylation27 BeadChip. DNA methylation was compared to gene expression, chromosomal alterations and clinicopathological parameters. Primary MCL displayed a heterogeneous methylation pattern dominated by DNA hypomethylation when compared to normal lymphoid samples. A total of 454 hypermethylated and 875 hypomethylated genes were identified as differentially methylated in at least 10% of primary MCL. Annotation analysis of hypermethylated genes recognized WNT pathway inhibitors and several tumor suppressor genes as frequently methylated, and a substantial fraction of these genes (22%) showed a significant downregulation of their transcriptional levels. Furthermore, we identified a subset of tumors with extensive CpG methylation that had an increased proliferation signature, higher number of chromosomal alterations and poor prognosis. Our results suggest that a subset of MCL displays a dysregulation of DNA methylation characterized by the accumulation of CpG hypermethylation highly associated with increased proliferation that may influence the clinical behavior of the tumors.<\/jats:p>","DOI":"10.1002\/ijc.28321","type":"journal-article","created":{"date-parts":[[2013,6,10]],"date-time":"2013-06-10T16:44:40Z","timestamp":1370882680000},"page":"2852-2863","source":"Crossref","is-referenced-by-count":18,"title":["Genome\u2010wide methylation analyses identify a subset of mantle cell lymphoma with a high number of methylated CpGs and aggressive clinicopathological features"],"prefix":"10.1002","volume":"133","author":[{"given":"Anna","family":"Enjuanes","sequence":"first","affiliation":[{"name":"Genomics Unit, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer, University of Barcelona Barcelona 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