POLD1 and cancer: These data show that the two POLD1 exonuclease mutated cancers have an extremely high mutation rate and share the shift in mutational spectrum with a previously reported hypermutable adenoma obtained from an individual with constitutional POLD1 S478N [6], suggesting a mutational process different from the mild mutagenesis observed in normal tissues of individuals with heterozygous POLD1 pathogenic variants.