Aberrant p15, p16, p53, and DAPK Gene Methylation in Myelomagenesis: Clinical and Prognostic Implications.
Clin Lymphoma Myeloma Leuk
; 16(12): 713-720.e2, 2016 12.
Article
in En
| MEDLINE
| ID: mdl-27622827
ABSTRACT
BACKGROUND:
Aberrant DNA methylation is considered a crucial mechanism in the pathogenesis of monoclonal gammopathies. We aimed to investigate the contribution of hypermethylation of 4 tumor suppressor genes to the multistep process of myelomagenesis.METHODS:
The methylation status of p15, p16, p53, and DAPK genes was evaluated in bone marrow samples from 94 patients at diagnosis monoclonal gammopathy of uncertain significance (MGUS) (n = 48), smoldering multiple myeloma (SMM) (n = 8) and symptomatic multiple myeloma (MM) (n = 38), and from 8 healthy controls by methylation-specific polymerase chain reaction analysis.RESULTS:
Overall, 63% of patients with MM and 39% of patients with MGUS presented at least 1 hypermethylated gene (P < .05). No aberrant methylation was detected in normal bone marrow. The frequency of methylation for individual genes in patients with MGUS, SMM, and MM was p15, 15%, 50%, 21%; p16, 15%, 13%, 32%; p53, 2%, 12,5%, 5%, and DAPK, 19%, 25%, 39%, respectively (P < .05). No correlation was found between aberrant methylation and immunophenotypic markers, cytogenetic features, progression-free survival, and overall survival in patients with MM.CONCLUSIONS:
The current study supports a relevant role for p15, p16, and DAPK hypermethylation in the genesis of the plasma cell neoplasm. DAPK hypermethylation also might be an important step in the progression from MGUS to MM.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Paraproteinemias
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Tumor Suppressor Protein p53
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DNA Methylation
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinase Inhibitor p15
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Death-Associated Protein Kinases
Type of study:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Clin Lymphoma Myeloma Leuk
Journal subject:
NEOPLASIAS
Year:
2016
Document type:
Article