Hamartomatous polyposis syndromes: molecular genetics, neoplastic risk, and surveillance recommendations.

Abstract

UNLABELLED:

Hamartomatous polyposis syndromes are characterized by an overgrowth of cells or tissues native to the area in which they normally occur. Juvenile polyposis syndrome (JPS) results from germ-line mutations in the SMAD-4 gene (18q21.1) that encodes for an enzyme involved in transforming growth factor beta(TGF-beta) signal transduction. The increased neoplastic risk may result from SMAD-4 mutations in the stromal component, which stimulate epithelial dysplasia and progression to invasive malignancy. Peutz-Jeghers syndrome (PJS) is associated with germ-line mutations in the LKB1 gene (19p13.3) that encodes a multifunctional serine-threonine kinase. These mutations occur in the epithelial component, suggesting a direct tumor suppressor effect. Patients are at an increased risk of intestinal and extraintestinal malignancies, including breast, pancreatic, ovarian, testicular, and cervical cancer. Cowden's disease is associated with germ-line mutations in the PTEN gene (10q22-23) and an increased risk of breast and thyroid malignancies. Ruvalcaba-Myhre-Smith syndrome is less common; controversy suggests that it may represent a variant of Cowden's disease.

CONCLUSIONS:

Genetic alterations underlying hamartomatous polyposis syndromes are diverse. Carcinogenesis may result from either germ-line mutations in the stroma (JPS) or as a direct result of functional deletion of tumor suppressor genes (PJS). Diagnosis depends on clinical presentation and patterns of inheritance within families. Suggested surveillance guidelines for the proband and first-degree relatives are outlined.

• Authors: D A Wirtzfeld, N J Petrelli, M A Rodriguez-Bigas
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 8 Issue 4 Pg. 319-27 (May 2001) ISSN: 1068-9265 [Print] United States
• PMID: 11352305 (Publication Type: Journal Article, Review)

Chemical References

• Transforming Growth Factor beta

Topics

• Adenomatous Polyposis Coli (complications, diagnosis, genetics)
• Adolescent
• Adult
• Age of Onset
• Aged
• Cell Transformation, Neoplastic
• Diagnosis, Differential
• Female
• Genes, Tumor Suppressor (genetics)
• Germ-Line Mutation
• Hamartoma Syndrome, Multiple (complications, diagnosis, genetics)
• Humans
• Male
• Middle Aged
• Neoplasm Invasiveness
• Pedigree
• Peutz-Jeghers Syndrome (complications, diagnosis, genetics)
• Point Mutation
• Risk Factors
• Signal Transduction
• Transforming Growth Factor beta (biosynthesis, genetics)