Abstract | BACKGROUND AND OBJECTIVES: DESIGN AND METHODS: Three hundred and seventeen B-cell malignancies were investigated by methylation-specific polymerase chain reaction (MSP) of MGMT, GSTP1, DAP-k, CASP8 and p73 genes. In selected cases, MSP results were matched to protein expression studies by immunohistochemistry or Western blotting. RESULTS: INTERPRETATION AND CONCLUSIONS: Methylation of MGMT, DAP-k and GSTP1 represents a major pathogenetic event in several B-cell malignancies. In follicular lymphoma and MALT lymphoma, frequent inactivation of the apoptosis extrinsic pathway through DAP-k methylation may reinforce the survival advantage already conferred by deregulation of the intrinsic apoptotic pathway. Inactivation of GSTP1 in gastric MALT lymphoma represents an additional mechanism favoring accumulation of reactive oxygen species and lymphomagenesis. Finally, the frequency of GSTP1 aberrant methylation in diffuse large B-cell lymphoma prompts studies aimed at verifying the prognostic impact of this epigenetic lesion in these lymphomas.
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Authors | Davide Rossi, Daniela Capello, Annunziata Gloghini, Silvia Franceschetti, Marco Paulli, Kishor Bhatia, Giuseppe Saglio, Umberto Vitolo, Stefano A Pileri, Manel Esteller, Antonino Carbone, Gianluca Gaidano |
Journal | Haematologica
(Haematologica)
Vol. 89
Issue 2
Pg. 154-64
(Feb 2004)
ISSN: 1592-8721 [Electronic] Italy |
PMID | 15003890
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Apoptosis Regulatory Proteins
- DNA-Binding Proteins
- Nuclear Proteins
- TP73 protein, human
- Tumor Protein p73
- Tumor Suppressor Proteins
- O(6)-Methylguanine-DNA Methyltransferase
- Acyltransferases
- Death-Associated Protein Kinases
- Calcium-Calmodulin-Dependent Protein Kinases
- fatty acyl ethyl ester synthase
- CASP8 protein, human
- Caspase 8
- Caspases
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Topics |
- Acyltransferases
(genetics)
- Aneuploidy
- Apoptosis
(genetics)
- Apoptosis Regulatory Proteins
- Blast Crisis
(genetics)
- Calcium-Calmodulin-Dependent Protein Kinases
(genetics)
- Caspase 8
- Caspases
(genetics)
- Cell Cycle
(genetics)
- CpG Islands
- DNA Methylation
- DNA Repair
(genetics)
- DNA-Binding Proteins
(genetics)
- Death-Associated Protein Kinases
- Disease Progression
- Follow-Up Studies
- Gene Silencing
- Genes, Tumor Suppressor
- Humans
- Inactivation, Metabolic
(genetics)
- Leukemia, B-Cell
(classification, genetics, pathology)
- Lymphoma, B-Cell
(classification, genetics, pathology)
- Nuclear Proteins
(genetics)
- O(6)-Methylguanine-DNA Methyltransferase
(genetics)
- Promoter Regions, Genetic
(genetics)
- Tumor Protein p73
- Tumor Suppressor Proteins
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