AUTHOR=Coppedè Fabio , Ricciardi Roberta , Lopomo Angela , Stoccoro Andrea , De Rosa Anna , Guida Melania , Petrucci Loredana , Maestri Michelangelo , Lucchi Marco , Migliore Lucia 

TITLE=Investigation of MLH1, MGMT, CDKN2A, and RASSF1A Gene Methylation in Thymomas From Patients With Myasthenia Gravis

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=13

YEAR=2020

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2020.567676

DOI=10.3389/fnmol.2020.567676

ISSN=1662-5099

ABSTRACT=<p>A feature of thymomas is their frequent association with myasthenia gravis (MG), an autoimmune disease characterized by the production of autoantibodies directed to different targets at the neuromuscular junction. Indeed, almost 30–40% of thymomas are found in patients with a type of MG termed thymoma-associated MG (TAMG). Recent studies suggest that TAMG-associated thymomas could represent a molecularly distinct subtype of thymic epithelial tumors (TETs), but few data are still available concerning the epigenetic modifications occurring in TAMG tissues. The promoter methylation levels of DNA repair (<italic>MLH1</italic> and <italic>MGMT</italic>) and tumor suppressor genes (<italic>CDKN2A</italic> and <italic>RASSF1A</italic>) have been frequently investigated in TETs, but methylation data in TAMG tissues are scarce and controversial. To further address this issue, we investigated <italic>MLH1</italic>, <italic>MGMT</italic>, <italic>CDKN2A</italic>, and <italic>RASSF1A</italic> methylation levels in blood samples and surgically resected thymomas from 69 patients with TAMG and in the adjacent normal thymus available from 44 of them. Promoter methylation levels of <italic>MLH1</italic>, <italic>MGMT</italic>, <italic>CDKN2A</italic>, and <italic>RASSF1A</italic> genes were not increased in cancer with respect to healthy tissues and did not correlate with the histological or pathological features of the tumor or with the MG symptoms. The present study suggests that hypermethylation of these genes is not frequent in TAMG tissues.</p>