SMAD4 and neoplasm: As mentioned above, although the mutational burden of PDAC is low compared with other solid tumor types [54,55], mutations in four major driver genes, namely, KRAS, TP53, CDKN2A, and SMAD4 [39,40,41], have also been identified, and the multistep accumulation of mutations during tumor progression have been investigated in detail [39,40,52,53].