SMAD4 and cancer: Additional somatic mutations in cancer-associated genes included mutations in K-ras (G12D), NF1 (R652C), TP53 (R175H), IRF2 (p.R82S), TCF7L2 (p.A418Tfs∗14), and SMAD4 (p.L43F) and a copy loss of SMAD4 (Fig. 4).