SMAD4 and pancreatic neoplasm: Interrogations of the Cancer Genome Atlas (TCGA) databases using the cBioPortal for Cancer Genomics also revealed major mutations and deletions in the activin/TGF signaling axes (deep deletion and truncating mutations >> amplification of unknown significance) (Table 2 and Figure 2) [119,122,123], indicating that inactivating alterations in these genes (ACVR1B, ACVR2A, ACVR2B, SMAD2, SMAD3, SMAD4, TGFBR1, TGFBR2) offer selection advantages in pancreatic tumor clonal evolution.