CDKN2A and cancer: Since p16/CDKN2A and BRCA2 mutations are not detected in the earliest sporadic premalignant pancreatic lesions and are more commonly found in later intermediate and advanced PanIN lesions, supports the hypothesis that these changes likely accumulate and impact the malignant progression of precursor lesions into PDAC rather than participate in cancer initiation (Hezel et al., 2006).