The Methylation of the p53 Targets the Genes , , and in the Tumor Tissue of Diffuse Large B-Cell Lymphoma.

The regulation of oncogenes by microRNA is a focus of medical research. hsa-miR-203, hsa-mir-129, hsa-miR-34a, hsa-miR-34b and hsa-miR-34c are oncosuppressive microRNAs that mediate the antitumor activity of p53. We seek to evaluate the frequencies, co-occurrence and clinical significance of the methylation of the , , and genes in the tumor tissue of diffuse large B-cell lymphoma (DLBCL). The methylation was assessed in 73 samples of DLBCL and in 11 samples of lymph nodes of reactive follicular hyperplasia by Methyl-Specific Polymerase Chain Reaction (MS-PCR) and Methylation-Sensitive High-Resolution-Melting (MS-HRM) methods. All four studied genes were not methylated in the tissue of reactive lymphatic nodes. The methylation frequencies of the , , and genes in lymphoma tissue were 67%, 66%, 27% and 62%, respectively. Co-occurrence of , and genes methylation, as well as the methylation of and pair genes were detected. The gene methylation was associated with increased International Prognostic Index (IPI) ( = 0.002), whereas the ( = 0.026) and ( = 0.011) genes' methylation was connected with Ki-67 expression level in tumor tissue at more than 45%. We found an increasing frequency of detection of gene methylation in the group of patients with the Germinal-Center B-cell like (GCB-like) subtype of DLBCL ( = 0.046). There was a trend towards a decrease in the remission frequency after the first line of therapy ( = 0.060) and deterioration in overall survival (OS) ( = 0.162) in patients with DLBCL with methylation of the promoter. The methylation of the , , and genes in DLBCL is tumor-specific and occurs in combination. The methylation of the studied genes may be a potential differential diagnostic biomarker to distinguish between lymphoma and reactive lymph nodes, while its independent predictive value has not been confirmed yet.