MGMT and neoplasm: In two seminal papers published in 2005 [10, 11], Stupp et al. and Hegi et al. established that the inactivation of the MGMT gene by DNA methylation in the tumor is associated with better survival in GB patients treated with TMZ and radiotherapy compared to the patients with unmethylated MGMT. Hypermethylation of MGMT occurs also in primary GB; however, it is a characteristic feature of secondary glioblastoma and is the “iceberg tip” of a more extensive alteration of the DNA methylation status known as “CpG island methylator phenotype” or CIMP.