We isolated DNA from microdissected gastrointestinal hamartomatous polyps in the PJS patient and investigated the loss of heterozygosity (LOH) at the LKB1 locus by real-time fluorescence polymerase chain reaction genotyping using a fluorescent resonance energy transfer technique.
These results suggest that gastrointestinal hamartomatous polyps in PJS patients develop through inactivation of the LKB1 gene by germ-line mutation plus somatic mutation or LOH of the unaffected LKB1 allele, and that additional mutations of the beta-catenin gene and p53 gene convert hamartomatous polyps into adenomatous and carcinomatous lesions.
Germline mutations of the STK11 gene mapped to chromosome 19p13.3 are responsible for Peutz Jeghers syndrome (PJS), a dominant disorder associated with characteristic gastrointestinal hamartomatous polyps and a predisposition to various cancers.