fig1

Figure 1. Temporal occurrence of signature mutations in pancreatic cancer and its effect on G1 to S transition. Driver mutations occur in KRAS of normal pancreatic cells initiating tumor formation. These mutations promote cell proliferation by upregulating cyclin D1. During the stages of low grade PanIN, INK4A mutations are acquired. It inactivates p16 tumor suppressor. As the tumor progresses to high grade PanIN, TP53 and SMAD4 are mutated mediating the inactivation of p21 and p27 CKIs. All these events deregulate G1 to S transition promoting uncontrolled proliferation and pancreatic cancer proceeds to full blown adenocarcinoma.