The hypermutator phenotype is defined not merely by mutation (which can reach up to ultra-hypermutator > 200 Mut/Mb) but by the overwhelming enrichment of SBS11 and related signatures (SBS119) indicative of TMZ mutagenesis; recent analyses from the GLASS consortium, encompassing 206 IDH-mutant gliomas with paired primary and recurrent samples, demonstrated enrichment for SBS11 and SBS119 signatures after TMZ treatment in both astrocytoma and oligodendroglioma subtypes [14,27]. This evidence concerns the gene IDH1 and central nervous system cancer.