title: 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 (MTHFR) and DNA methylation (DNMT1,DNMT3A, andDNMT3B) 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. BothMTHFRandDNMT3Apromoters showed significantly higher methylation in tumor tissue with respect to blood, andMTHFRalso showed significantly higher methylation levels in tumor tissue respect to healthy adjacent thymic epithelial cells. BothDNMT1andDNMT3Bpromoter regions were mostly hypomethylated in all the investigated tissues. The present study suggests thatMTHFRmethylation is increased in thymomas obtained from MG patients; furthermore, some degrees of methylation of theDNMT3Agene were observed in thymic tissue with respect to blood.
authors.affiliation: 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. angela.lopomo@student.unisi.it.|Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy. angela.lopomo@student.unisi.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Lopomo
authors.affiliation: Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy. r.ricciardi@ao-pisa.toscana.it.|Division of Thoracic Surgery, Cardiothoracic and Vascular Surgery Department, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy. r.ricciardi@ao-pisa.toscana.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ricciardi
authors.affiliation: Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy. michelangelo.mvg@tin.it.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Maestri
authors.affiliation: Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy. annu.derosa@hotmail.it.
authors.forename: Anna
authors.initials: A
authors.lastname: De Rosa
authors.affiliation: Division of Thoracic Surgery, Cardiothoracic and Vascular Surgery Department, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy. franca.mamelfi@gmail.com.
authors.forename: Franca
authors.initials: F
authors.lastname: Melfi
authors.affiliation: Division of Thoracic Surgery, Cardiothoracic and Vascular Surgery Department, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy. marco.lucchi@unipi.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Lucchi
authors.affiliation: Division of Thoracic Surgery, Cardiothoracic and Vascular Surgery Department, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy. a.mussi@dc.med.unipi.it.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mussi
authors.affiliation: 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. fabio.coppede@med.unipi.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Coppedè
authors.affiliation: 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. lucia.migliore@med.unipi.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Migliore
mesh_terms: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009157:Myasthenia Gravis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D013945:Thymoma / Q000235:genetics*; D013950:Thymus Gland / Q000473:pathology; D013953:Thymus Neoplasms / Q000235:genetics*; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C573423:MTHFR protein, human; C000619380:DNMT1 protein, human
keywords: DNA methylation; DNMT3A; MTHFR; cancer; epigenetics; myasthenia gravis; thymoma