In conclusion, we employed ectopic expression of p16 WT and L16R in pancreatic cancer cells, and normal fibroblasts derived from individuals in families that segregate p16-L16R to provide molecular evidence that p16-L16R is a deleterious mutation with little ability to interact with CDK4/6 or suppress cell cycle progression. This evidence concerns the gene CDKN2A and pancreatic neoplasm.