Frequent aberrant promoter hypermethylation of O6-methylguanine-DNA methyltransferase and death-associated protein kinase genes in immunodeficiency-related lymphomas

Davide Rossi; Gianluca Gaidano; Annunziata Gloghini; Clara Deambrogi; Silvia Franceschetti; Eva Berra; Michaela Cerri; Chiara Vendramin; Annarita Conconi; Alessandra Viglio; Giuliana Muti; Pierluigi Oreste; Enrica Morra; Marco Paulli; Daniela Capello; Antonino Carbone

doi:10.1046/j.1365-2141.2003.04644.x

Frequent aberrant promoter hypermethylation of O6-methylguanine-DNA methyltransferase and death-associated protein kinase genes in immunodeficiency-related lymphomas

Br J Haematol. 2003 Nov;123(3):475-8. doi: 10.1046/j.1365-2141.2003.04644.x.

Authors

Davide Rossi¹, Gianluca Gaidano, Annunziata Gloghini, Clara Deambrogi, Silvia Franceschetti, Eva Berra, Michaela Cerri, Chiara Vendramin, Annarita Conconi, Alessandra Viglio, Giuliana Muti, Pierluigi Oreste, Enrica Morra, Marco Paulli, Daniela Capello, Antonino Carbone

Affiliation

¹ Department of Medical Sciences & IRCAD, Haematology Unit, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.

PMID: 14617009
DOI: 10.1046/j.1365-2141.2003.04644.x

Abstract

Aberrant promoter hypermethylation is a mechanism of tumour suppressor gene inactivation. We explored aberrant promoter hypermethylation of multiple genes in 88 human immunodeficiency virus (HIV)-non Hodgkin lymphomas (NHL), 25 post-transplant lymphoproliferative disorders (PTLD) and five common variable immunodeficiency (CVI)-related NHL. Twenty-six of 79 (32.9%) HIV-NHL, eight of 14 (57.1%) PTLD and two of five (40.0%) CVI-NHL showed aberrant hypermethylation of O6-methylguanine-DNA methyltransferase (MGMT). Aberrant hypermethylation of death-associated protein-kinase (DAP-K) occurred in 70 of 84 (83.3%) HIV-NHL, 19 of 25 (72.0%) PTLD and three of five (60.0%) CVI-NHL. These data implicate MGMT and DAP-K hypermethylation in lymphomagenesis of immunodeficient hosts. In particular, promoter hypermethylation of DAP-K represents the most frequent molecular alteration yet identified in immunodeficiency-related lymphomas.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis Regulatory Proteins
Burkitt Lymphoma / genetics
Calcium-Calmodulin-Dependent Protein Kinases / genetics
Caspase 8
Caspase 9
Caspases / genetics
Central Nervous System Neoplasms / genetics
Common Variable Immunodeficiency / complications
Common Variable Immunodeficiency / genetics*
DNA Methylation*
DNA-Binding Proteins / genetics
Death-Associated Protein Kinases
Genes, Tumor Suppressor
Humans
Lymphoma, AIDS-Related / genetics*
Lymphoma, B-Cell / genetics
Lymphoma, Large B-Cell, Diffuse / genetics
Lymphoma, Non-Hodgkin / genetics*
Lymphoma, Non-Hodgkin / immunology
Lymphoma, T-Cell / genetics
Multiple Myeloma / genetics
Nuclear Proteins / genetics
O(6)-Methylguanine-DNA Methyltransferase / genetics*
Promoter Regions, Genetic*
Tumor Protein p73
Tumor Suppressor Proteins

Substances

Apoptosis Regulatory Proteins
DNA-Binding Proteins
Nuclear Proteins
Tumor Protein p73
Tumor Suppressor Proteins
O(6)-Methylguanine-DNA Methyltransferase
Death-Associated Protein Kinases
Calcium-Calmodulin-Dependent Protein Kinases
CASP8 protein, human
CASP9 protein, human
Caspase 8
Caspase 9
Caspases