Gene-Specific Methylation Analysis in Thymomas of Patients with Myasthenia Gravis

Abstract

Thymomas are uncommon neoplasms that arise from epithelial cells of the thymus and are often associated with myasthenia gravis (MG), an autoimmune disease characterized by autoantibodies directed to different targets at the neuromuscular junction. Little is known, however, concerning epigenetic changes occurring in thymomas from MG individuals. To further address this issue, we analyzed DNA methylation levels of genes involved in one-carbon metabolism (<i>MTHFR</i>) and DNA methylation (<i>DNMT1</i>, <i>DNMT3A</i>, and <i>DNMT3B</i>) in blood, tumor tissue, and healthy thymic epithelial cells from MG patients that underwent a surgical resection of a thymic neoplasm. For the analyses we applied the methylation-sensitive high-resolution melting technique. Both <i>MTHFR</i> and <i>DNMT3A</i> promoters showed significantly higher methylation in tumor tissue with respect to blood, and <i>MTHFR</i> also showed significantly higher methylation levels in tumor tissue respect to healthy adjacent thymic epithelial cells. Both <i>DNMT1</i> and <i>DNMT3B</i> promoter regions were mostly hypomethylated in all the investigated tissues. The present study suggests that <i>MTHFR</i> methylation is increased in thymomas obtained from MG patients; furthermore, some degrees of methylation of the <i>DNMT3A</i> gene were observed in thymic tissue with respect to blood.