The definitional criteria we propose for this unique subtype is a de novo/primary treatment-naïve IDH-wildtype and histone H3-wildtype glioblastoma occurring in an adult with next-generation DNA sequencing demonstrating somatic hypermutation and biallelic inactivation of a canonical mismatch repair gene (MSH2, MSH6, MLH1, or PMS2) via gene deletion, truncating mutation, or known pathogenic missense mutation. This evidence concerns the gene MSH6 and glioblastoma.