POLD1 and neoplasm: In one case with high signature D1 activity, there was no exonuclease mutation, but the tumor did have an L606M mutation in the POLD1 polymerase domain (Fig. 4c, d), which had been shown in vitro to increase polymerase delta error rate21 and had also been observed in hypermutated glioblastomas with germline biallelic mismatch repair deficiency8,9.