Figure 1

Model of the genetic progression of pancreatic carcinogenesis. The genetic alterations that occur during pancreatic carcinogenesis can be classified as early (activating mutation of KRAS), intermediate (inactivation of CDKN2A), and late (inactivation of TP53 and SMAD4 and activation of some pathways in PCSCs) events. Markers of PCSCs, including CD24, CD44, CXCR4, ESA, and Nestin, are detected in different sites during pancreatic carcinogenesis (in order of increasing percentage): normal ducts, low-grade PanIN lesions, high-grade PanIN lesions, and PDACs. FOXM1 may play a critical role in the early stages of PDAC development via cross-talk with major signaling pathways. Other gene mutations may occur during PanIN formation but are not illustrated in this model.