MGMT and central nervous system cancer: Next we sought to address how the HOX-signature was related to three established molecular GBM classification schemes: (1) the four GBM expression subtypes neural, proneural, mesenchymal, and classical as proposed by Verhaak and colleagues [21]; (2) the glioma CpG island methylator phenotype (G-CIMP) present in a subgroup of proneural GBM [22]; or (3) distinction of MGMT promoter methylated vs. unmethylated that has been shown to be highly predictive for benefit from alkylating agent chemotherapy [23].