Frequent aberrant promoter hypermethylation of O6-methylguanine-DNA methyltransferase and death-associated protein kinase genes in immunodeficiency-related lymphomas.
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.
Rossi
Davide
D
Department of Medical Sciences & IRCAD, Haematology Unit, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
Gaidano
Gianluca
G
Gloghini
Annunziata
A
Deambrogi
Clara
C
Franceschetti
Silvia
S
Berra
Eva
E
Cerri
Michaela
M
Vendramin
Chiara
C
Conconi
Annarita
A
Viglio
Alessandra
A
Muti
Giuliana
G
Oreste
Pierluigi
P
Morra
Enrica
E
Paulli
Marco
M
Capello
Daniela
D
Carbone
Antonino
A
D051017:Apoptosis Regulatory Proteins; D002051:Burkitt Lymphoma / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000235:genetics; D016543:Central Nervous System Neoplasms / Q000235:genetics; D017074:Common Variable Immunodeficiency / Q000150:complications / Q000235:genetics*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D064550:Death-Associated Protein Kinases; D016147:Genes, Tumor Suppressor; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000235:genetics; D009101:Multiple Myeloma / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011401:Promoter Regions, Genetic; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D019853:O(6)-Methylguanine-DNA Methyltransferase; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases