title: Hypermethylation of p15 gene in diffuse - large B-cell lymphoma: association with less aggressiveness of the disease.
abstract: In this study, methylation-specific polymerase chain reaction was used to investigate the potential prognostic significance of the methylation status of p15, p16, MGMT, and DAPK genes in 51 specimens of diffuse large B-cell lymphoma (DLBCL). Hypermethylation of p15 gene was significantly more prevalent in patients without relapse (p = 0.001) and there was a trend toward more frequent presence of p15 methylation in patients without death outcome within 5-year follow-up period (p = 0.086) Also, there was a trend toward accumulation of p15 methylation with favorable clinicopathological parameters including: age ≤ 60 years (p = 0.091), normal levels of lactate dehydrogenase (p = 0.090), Eastern Cooperative Oncology Group performance status < 2 (p = 0.095), and low/intermediate low International Prognostic Index (p = 0.076). In the female group and group of the patients without bulky tumor mass, treated with chemotherapeutic regimens including rituximab, methylation of p15 was significantly related to longer overall survival (p = 0.036 and 0.027, respectively). Our results suggest that promoter methylation of p15 gene could have prognostic value in DLBCL patients treated with rituximab when used in combination with gender and tumor size.
authors.affiliation: University of Belgrade-Vinča Institute of Nuclear Sciences, Belgrade, Serbia.
authors.forename: Milena
authors.initials: M
authors.lastname: Krajnović
authors.forename: Maja Peruničić
authors.initials: MP
authors.lastname: Jovanović
authors.forename: Biljana
authors.initials: B
authors.lastname: Mihaljević
authors.forename: Boško
authors.initials: B
authors.lastname: Anđelić
authors.forename: Olivera
authors.initials: O
authors.lastname: Tarabar
authors.forename: Slavica
authors.initials: S
authors.lastname: Knežević-Ušaj
authors.forename: Koviljka
authors.initials: K
authors.lastname: Krtolica
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D064550:Death-Associated Protein Kinases / Q000235:genetics; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D000069283:Rituximab; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025521:Tumor Suppressor Proteins; D000069283:Rituximab; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D045643:DNA Repair Enzymes
keywords: diffuse large B-cell lymphoma; methylation; p15; prognosis; rituximab