SMAD4 and neoplasm: Initiation of PanIN formation involves dysregulation of critical signaling pathways and processes including DNA damage response (TP53 (tumor protein p53)), cell cycle regulation (CDKN2A (cyclin-dependent kinase inhibitor 2A)—act as tumor suppressors by regulating inhibition of the cell cycle) and transforming growth factor β (TGFβ) signaling mediated by SMAD4 (SMAD4 (suppressor of mothers against decapentaplegic 4)).