CDKN2A and metastatic neoplasm: Malignant progression from pancreatic intra-epithelial neoplasia (PanINs) to invasive and metastatic disease is usually accompanied by early acquisition of activating mutations in the KRAS oncogene, which occurs in >90% of all PDAC cases, followed by loss of tumor suppressors such as INK4A/ARF, TP53, and SMAD43.