To explore the dynamics of combined p16 biallelic inactivation and Kras activation in pancreatic tumor development and progression in the setting of intact p19, p16−/−; LSL- KrasG12D; Pdx1-Cre mice and p16flox/flox; LSL- KrasG12D; Pdx1-Cre mice were generated and characterized. Here, CDKN2A is linked to pancreatic neoplasm.