SMAD4 and familial pancreatic carcinoma: In this regard, a review of pancreas tumor specimens within the Catalogue of Somatic Mutations in Cancer (COSMIC) database reveals that most pancreatic cancers harbor somatic mutations (Table 2), with the five most frequent aberrations being KRAS, TP53, CDKN2A, SMAD4, and ARID1A. [22, 23] If specific “actionable” mutations can drive marked improvements in survival in melanoma and NSCLC, similar opportunities might reasonably be expected in pancreatic cancer.