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MGMT and Whole-Genome DNA Methylation Impacts on Diagnosis,Prognosis and Therapy of Glioblastoma Multiforme
Authors:Rosa Della Monica  Mariella Cuomo  Michela Buonaiuto  Davide Costabile  Raduan Ahmed Franca  Marialaura Del Basso De Caro  Giuseppe Catapano  Lorenzo Chiariotti  Roberta Visconti
Abstract:Epigenetic changes in DNA methylation contribute to the development of many diseases, including cancer. In glioblastoma multiforme, the most prevalent primary brain cancer and an incurable tumor with a median survival time of 15 months, a single epigenetic modification, the methylation of the O6-Methylguanine-DNA Methyltransferase (MGMT) gene, is a valid biomarker for predicting response to therapy with alkylating agents and also, independently, prognosis. More recently, the progress from single gene to whole-genome analysis of DNA methylation has allowed a better subclassification of glioblastomas. Here, we review the clinically relevant information that can be obtained by studying MGMT gene and whole-genome DNA methylation changes in glioblastomas, also highlighting benefits, including those of liquid biopsy, and pitfalls of the different detection methods. Finally, we discuss how changes in DNA methylation, especially in glioblastomas bearing mutations in the Isocitrate Dehydrogenase (IDH) 1 and 2 genes, can be exploited as targets for tailoring therapy.
Keywords:glioblastoma multiforme   MGMT gene methylation   whole-genome methylation profiling   liquid biopsy   IDH1/2 mutations
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