SMAD4 and pancreatic neoplasm: Analyzing a region of chromosome 18q which has been found to be frequently lost in pancreatic cancers led to the identification of SMAD4 and the elucidation of its role in tumorigenesis (44), which was supported by the observation that germ-line SMAD4 mutations cause juvenile polyposis (JP), a condition which is characterized by the formation of intestinal polyps at young age and a cumulative lifetime risk for gastrointestinal cancer of 50% (62).