In a prospective study examining 63 patients diagnosed with malignant glioma, Kreth et al. identified MGMT mRNA expression as a predictor of clinical outcome independent from MGMT promoter methylation underscoring the necessity of approaching MGMT biology more comprehensively and also elucidating methylation-independent mechanisms that may regulate MGMT expression [30]. This evidence concerns the gene MGMT and malignant glioma.