POLD1 and neoplasm: The mutational spectrum of the tumor also differed from the spectrum identified in the cultured fibroblasts of POLD1 L474P heterozygous carriers and in the phenotypically normal crypts of carriers of different POLD1 pathogenic variants studied by Robinson et al. [6] Specifically, the tumor sequence was enriched in C>A mutations (which comprised ~54% of observed mutations), particularly in TpCpA and TpCpT contexts (Fig. 3B).