The occurrence of this mutation may be the initial step in the tumorigenesis of pancreatic cancer, leading to the genomic instability indispensable for the sequential inactivation of suppressor genes such as p53, p16 (CDKN2A/INK4A), and DPC4 (SMAD4/DPC4) [9]. This evidence concerns the gene SMAD4 and familial pancreatic carcinoma.