title: Prognostic significance of epigenetic inactivation of p16, p15, MGMT and DAPK genes in follicular lymphoma.
abstract: In this study, methylation-specific polymerase chain reaction was used to investigate the role and potential prognostic significance of the methylation status of p16, p15, MGMT and DAPK genes in 32 specimens of follicular lymphoma (FL). Hypermethylation of p15 gene was associated with lower hemoglobin level (P = 0.020) and MGMT/DAPK comethylation with relapsed disease (P = 0.018). Among all patients with FL, there was no significant difference in the overall survival between those with hypermethylated and unmethylated of any examined genes. Therefore, we analyzed methylation in the different groups according to FL International Prognostic Index (FLIPI) and tumor grade. In the high-risk group, patients with hypermethylated p16 gene had significant lower overall survival than those with unmethylated p16 (P = 0.006) and trend toward shorter failure-free survival (P = 0.068). In the same risk group, there was a trend toward longer overall survival for patients with hypermethylated MGMT gene, compared to those with unmethylated MGMT gene (P = 0.066). p15 methylation had impact on shorter overall survival in grade I group of patients (P = 0.013), and DAPK methylation tended to have impact on shorter failure-free survival in the whole examined group (P = 0.079). Our results suggest that promoter methylation of p16 and MGMT genes could have prognostic value when used in combination with the FLIPI and p15 methylation in combination with tumor grade. Concurrent methylation of MGMT and DAPK genes could be the marker of tumor chemoresistance and disease recurrence.
authors.affiliation: Institute of Nuclear Sciences "Vinča", University of Belgrade, 11001 Belgrade, Serbia. lena2mkd@yahoo.com
authors.forename: Milena
authors.initials: M
authors.lastname: Krajnović
authors.forename: Milica
authors.initials: M
authors.lastname: Radojković
authors.forename: Radoslav
authors.initials: R
authors.lastname: Davidović
authors.forename: Bogomir
authors.initials: B
authors.lastname: Dimitrijević
authors.forename: Koviljka
authors.initials: K
authors.lastname: Krtolica
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D064550:Death-Associated Protein Kinases; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D005260:Female; D019942:Genes, p16; D006801:Humans; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D016133:Polymerase Chain Reaction; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D045643:DNA Repair Enzymes