Methylation of <i>p</i>16<sup>INK4A</sup> and Mitotic Arrest Defective Protein 2 (<i>MAD</i>2) Genes in Gastric Marginal-Zone B-Cell Lymphomas

Abstract

<i>Background:</i> Products of cyclin-dependent kinase inhibitor <i>p</i>16<sup>INK4A</sup>and mitotic arrest defective protein 2 (<i>MAD</i>2) 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 <i>p</i>16<sup>INK4A</sup> and <i>MAD</i>2 genes in gastric marginal-zone B-cell lymphoma (MZBCL). <i>Materials and Methods:</i> 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. <i>Results and Conclusion:</i><i>p</i>16<sup>INK4A</sup> was methylated in 30 of 40 MZBCLs (75%). The lymphomas with <i>p</i>16<sup>INK4A</sup> methylation tended to be negative for t(11;18)(q21;q21) (p = 0.011). <i>MAD</i>2 gene was methylated in 23 of 38 MZBCLs (61%). Lymphomas with <i>MAD</i>2 gene methylation more frequently expressed BCL10 (p = 0.037). These methylation profiles suggest that <i>p</i>16<sup>INK4A</sup> and <i>MAD</i>2 gene may play a role in the pathogenesis of MZBCL via different pathways; <i>MAD</i>2 gene is <i>Helicobacter pylori </i>independent with a close association with BCL10 while <i>p</i>16<sup>INK4A</sup> is <i>H. pylori</i> dependent with an inverse correlation with the t(11;18)(q21;q21) translocation.