POLD1 and central nervous system cancer: Glioma patients carrying rare POLE/POLD1 variants were primarily affected by glioblastoma CNS WHO grade 4 (6/11, 55%), astrocytoma CNS WHO grade 3 (2/11, 18%), astrocytoma CNS WHO grade 2 (2/11, 18%), and oligodendroglioma CNS WHO grade 2 (1/11, 9%) at a mean age of 48 years (range: 23–75 years), and with a mean overall survival of 59 months (range: 2-165 months) (Fig. 1; Table 2).