Gene regulation by methylation

Abstract

Epigenetic gene regulation of specific genes strongly affects clinical outcome of malignant glioma. MGMT is the best studied gene for the connection of promoter methylation and clinical course in glioblastoma. While MGMT promoter methylation analysis currently does not alter treatment of glioblastoma patients, mainly because of a lack of convincing therapy to radiotherapy and concomitant administration of alkylating drugs, there is increasing interest on the part of patients and physicians in having this molecular parameter assessed. This chapter gives a short overview of the physiological characteristics of the epigenome in normal cells and tissues and the changes in epigenetic gene regulation following malignant transformation. It discusses the technical aspects, advantages, and shortcomings of currently used approaches for single-gene and genome-wide methylation analyses. Finally, an outlook is given on potential therapeutic avenues and targets to overcome tumor-suppressor gene silencing by aberrant promoter methyla-tion in gliomas. © 2009 Springer Berlin Heidelberg.