Molecular Genetics of Peutz-Jegher Syndrome

摘要

Peutz-Jeghers Syndrome (PJS) is one of the inherited syndromes associated with polyposis. It is characterized by mucocutaneous pigmentation, especially in the vermilion border of the lips and gastrointestinal tract. This is known as hamartomatous polyposis. The disease results from an autosomal dominant mutation localized in the LKB1 (liver kinase B1) or STK11 (serine/threonine kinase 11) gene on chromosome 19p13.3. The STK11 gene plays a role as a tumor suppressor gene. Mutation in STK11 results in an abnormally shortened or truncated protein, transcriptional splicing errors, and loss of kinase activity. Therefore, somatic inactivation of STK11 will cause formation of hamartomas and tumors in PJS. Yoon et al. identified several types of STK11 gene mutation, including nonsense, missense, splicing site, and ameshift mutations. The other mutation STK11 lead to complications such as cancers, surgical treatment, and increased numbers of polyps. Another mechanism for the inactivation of tumor suppresor genes is promoter hypermethylation of normally unmethylated CpG islands located in promoter regions of DNA repair and tumor suppressor genes. In conclusion, STK11/LKB1 gene mutation is the etiology of PJS.