Enlarged nuclei or multinucleated cells were identified in 6/15 (40%) gliomas from patients with POLE/POLD1 variants, including a primary astrocytoma CNS WHO grade 2, a primary astrocytoma CNS WHO grade 3 and its recurrent tumor of the same grade, and three primary glioblastomas CNS WHO grade 4, two of which carried the POLE:c.776G>A p.(R259H) variant (Figs. 2c and 3c, Additional file 1: Table S3). Here, POLE is linked to central nervous system cancer.