Genome-wide methylation analyses identify a subset of mantle cell lymphoma with a high number of methylated CpGs and aggressive clinicopathological features
Enjuanes, A. (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Albero Gallego, Robert (Hospital Clínic i Provincial de Barcelona)
Clot, Guillem (Hospital Clínic i Provincial de Barcelona)
Navarro, Alba (Hospital Clínic i Provincial de Barcelona)
Bea, Sílvia (Hospital Clínic i Provincial de Barcelona)
Pinyol, Magda (Hospital Clínic i Provincial de Barcelona)
Martin-Subero, Jose Ignacio (Universitat de Barcelona)
Klapper, Wolfram (University Hospital Schleswig-Holstein)
Staudt, L.M. (National Cancer Institute, Bethesda, USA)
Jaffe, E.S. (National Cancer Institute, Bethesda, USA)
Rimsza, L.M. (University of Arizona College of Medicine)
Braziel, Rita M (Oregon Health and Science University)
Delabie, Jan (Rikshospitalet University Hospital Oslo)
Cook, James R. (Cleveland Clinic)
Tubbs, R.S.
Gascoyne, Randy (British Columbia Cancer Agency)
Connors, Joseph M (British Columbia Cancer Agency)
Weisenburger, Dennis D (University of Nebraska Medical Center)
Greiner, Timothy C (University of Nebraska Medical Center)
Chan, Wing-Chung (University of Nebraska Medical Center)
López Guillermo, Armando (Hospital Clínic i Provincial de Barcelona)
Rosenwald, Andreas (Institute of Pathology. University of Würzburg)
Ott, German (Robert-Bosch-Krankenhaus (Stuttgart, Alemanya))
Campo, Elias (Hospital Clínic i Provincial de Barcelona)
Jares, Pedro (Hospital Clínic i Provincial de Barcelona)

Data:	2013
Resum:	Mantle cell lymphoma (MCL) is a B-cell neoplasm with an aggressive clinical behavior characterized by the t(11;14)(q13;q32) and cyclin D1 overexpression. To clarify the potential contribution of altered DNA methylation in the development and/or progression of MCL, we performed genome-wide methylation profiling of a large cohort of primary MCL tumors (n = 132), MCL cell lines (n = 6) and normal lymphoid tissue samples (n = 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.
Ajuts:	Ministerio de Ciencia e Innovación SAF 2008/03630 Generalitat de Catalunya 2009/SGR-00992 Ministerio de Ciencia e Innovación PI11/01177 Ministerio de Ciencia y Educación BES-2007-16330)
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Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Matèria:	Mantle Cell Lymphoma ; Genome-wide ; Hypermethylation ; Hypomethylation ; Pathogenesis
Publicat a:	International Journal of Cancer, Vol. 133, Num. 12 (December 2013) , p. 2852-2863, ISSN 1097-0215

DOI: 10.1002/ijc.28321

Postprint 27 p, 414.3 KB

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