In addition to activating KRAS mutations, leading to increased proliferation, and telomere shortening, leading to chromosomal instability, the inactivation of three tumor suppressor genes (p16/CDKN2A, tumor protein 53 (TP53), and SMAD family member 4 (SMAD4/DPC4)) is relevant for the formation of pancreatic cancer. Here, SMAD4 is linked to pancreatic neoplasm.