While DNA mismatch repair (MMR) deficiency-associated mutational signatures SBS6, SBS15, SBS21, or SBS26 were identified in 13 of 14 (93%) glioma DNAs from 10 patients with rare POLE/POLD1 variants, a substantial (> 50%) contribution was detected in only 5 of 14 (36%) gliomas (Fig. 3b). Here, POLD1 is linked to central nervous system cancer.