Johnson et al. (2014) reported that the 4 patients identified in our current study as progressing to G-CIMP-low at recurrence (Figures 2 and S4E) harbored a signature of temozolomide (TMZ)-induced mutagenesis in the RB and AKT-mTOR pathways, following an alternative evolutionary path to GBM. Despite the fact that driver mutations in these pathways and the hypermutator phenotype can emerge at disease relapse after chemotherapy with TMZ (Johnson et al., 2014), we identified convergent genetic alterations in G-CIMP-low primary tumors (Ceccarelli et al., 2016; Figure S5). Here, AKT1 is linked to glioblastoma.