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Int. J. Mol. Sci. 2016, 17(12), 2121; doi:10.3390/ijms17122121

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

1
Department of Translational Research and New Technologies in Medicine and Surgery, Division of Medical Genetics, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy
2
Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
3
Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy
4
Division of Thoracic Surgery, Cardiothoracic and Vascular Surgery Department, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Li Yang
Received: 11 November 2016 / Revised: 6 December 2016 / Accepted: 12 December 2016 / Published: 16 December 2016
(This article belongs to the Special Issue Tumor Microenvironment and Metabolism)
View Full-Text   |   Download PDF [921 KB, uploaded 16 December 2016]   |  

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 (MTHFR) and DNA methylation (DNMT1, DNMT3A, and DNMT3B) 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 MTHFR and DNMT3A promoters showed significantly higher methylation in tumor tissue with respect to blood, and MTHFR also showed significantly higher methylation levels in tumor tissue respect to healthy adjacent thymic epithelial cells. Both DNMT1 and DNMT3B promoter regions were mostly hypomethylated in all the investigated tissues. The present study suggests that MTHFR methylation is increased in thymomas obtained from MG patients; furthermore, some degrees of methylation of the DNMT3A gene were observed in thymic tissue with respect to blood. View Full-Text
Keywords: thymoma; myasthenia gravis; cancer; epigenetics; DNA methylation; MTHFR; DNMT3A thymoma; myasthenia gravis; cancer; epigenetics; DNA methylation; MTHFR; DNMT3A
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MDPI and ACS Style

Lopomo, A.; Ricciardi, R.; Maestri, M.; De Rosa, A.; Melfi, F.; Lucchi, M.; Mussi, A.; Coppedè, F.; Migliore, L. Gene-Specific Methylation Analysis in Thymomas of Patients with Myasthenia Gravis. Int. J. Mol. Sci. 2016, 17, 2121.

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