SMAD4 and cancer: However, considering the classification of cancer cell signaling pathways i.e. cell fate, cell survival, and genome maintenance, it is striking that the additional mutations in the early onset EACs occurred mainly in genes classified in cell fate pathways (APC, CDH1, CTNNB1), while all additional mutations in conventional EACs were identified in genes classified in survival pathways (ABL1, GNA11, KRAS, MET, SMAD4, VHL, GNAS, FBXW7).