CDKN2A and neoplasm: Activation of other pathways by additional mutations, including mutations in tumor suppressor genes, such as TP53, one of the most frequently mutated genes in human cancer, CDKN2A, the gene encoding p16 and p14, and SMAD4 and/or environmental stimuli (obesity, type 2 diabetes mellitus) are required for the promotion of invasive PDAC.