Molecular and phenotypic markers of hamartomatous polyposis syndromes in the gastrointestinal tract

Hamartomatous gastrointestinal polyposis syndromes have always been conside red as nonneoplastic. Nevertheless, an increased cancer risk both within an d outside the gastrointestinal tract may exist in these syndromes. The hama rtomatous polyps may sometimes harbor dysplasia, but their neoplastic poten tial is unknown. The genetic defects causing the hamartomatous syndromes are less well estab lished than, for example, familial adenomatous polyposis (FAP) and heredita ry non-polyposis colorectal cancer (HNPCC). The genetic studies on the Mend elian inherited syndromes FAP and HNPCC have made a major contribution to t he identification of genes involved in colorectal tumorigenesis. The genes involved in colorectal cancer development may also contribute to cancer dev elopment in the hamartomatous polyposis syndromes, and are currently under investigation. Furthermore, new insights into the development of various ca ncers may be obtained by the isolation and characterization of genes involv ed in Mendelian inherited hamartomatous polyposis syndromes. This report summarizes the available literature on this subject, and descri bes the pheno- and genotypic features of the hamartomatous syndromes of juv enile polyposis, Peutz-Jeghers syndrome, and Cowden's disease.