Background: Products of cyclin-dependent kinase inhibitor p16INK4Aand mitotic arrest defective protein 2 (MAD2) genesare key regulator proteins at the G1 restriction point and mitotic checkpoint of the cell cycle. The objective of this study was to investigate the role of promoter methylation of p16INK4A and MAD2 genes in gastric marginal-zone B-cell lymphoma (MZBCL). Materials and Methods: Gastric biopsies from 40 patients were analyzed by methylation-specific polymerase chain reaction, and the methylation status was compared with the results of BCL10 expression and t(11;18)(q21;q21) translocation. Results and Conclusion:p16INK4A was methylated in 30 of 40 MZBCLs (75%). The lymphomas with p16INK4A methylation tended to be negative for t(11;18)(q21;q21) (p = 0.011). MAD2 gene was methylated in 23 of 38 MZBCLs (61%). Lymphomas with MAD2 gene methylation more frequently expressed BCL10 (p = 0.037). These methylation profiles suggest that p16INK4A and MAD2 gene may play a role in the pathogenesis of MZBCL via different pathways; MAD2 gene is Helicobacter pylori independent with a close association with BCL10 while p16INK4A is H. pylori dependent with an inverse correlation with the t(11;18)(q21;q21) translocation.

Keywords:
B cells, DNA methylation, Lymphomas, MAD2, Marginal-zone B-cell lymphoma, p16INK4A
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