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Epigenetic implications in the pathogenesis of corticotroph tumors
Ticiana Paes1,2, Leo J Hofland1, Anand M Iyer1
1Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, Rotterdam, GD 3015, The Netherlands.
Abstract:
Non-mutational epigenetic reprogramming is considered an important enabling characteristic of neoplasia. Corticotroph tumors and other subtypes of pituitary tumors are characterized by distinct epigenetic profiles. The DNA methylation profile is consistent with disease-specific gene expression, which highlights the importance of epigenetic changes in tumor formation and progression. Elucidating the epigenetic changes underlying tumorigenesis plays an important role in understanding the molecular pathogenesis of corticotroph tumors and may ultimately contribute to improving tumor-specific treatment. Here, we provide an overview of the epigenetic landscape of corticotroph tumors. We also review the role of epigenetics in silencing the expression of tumor suppressor genes and promoting oncogenes expression, which could potentially be involved in the pathogenesis of corticotroph tumors. We briefly discuss microRNAs and epigenetic aspects of POMC regulation. Lastly, since the epigenetic changes are reversible, we discuss drugs that target epigenetic modifiers that could potentially be used in the arsenal of Cushing's disease treatment modalities.
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