| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
Peutz-Jeghers syndrome(PJS) is characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous melanin deposition, and increased risk of cancer, mainly in the gastrointestinal tract We examined mutation of the LKB1, β-catenin, APC, K-ras, and p53 genes in 27 gastrointestinal hamartomatous polyps from 10 patients in nine PJS families. Of these hamartomatous polyps, one intestinal polyp had an adenomatous lesion, and one gastric polyp contained adenomatous and carcinomatous lesions. Germ line mutation of the LKB1 gene were detected in six PJS families. Somatic mutation of the LKB1 gene were found in 5 polyps. whereas loss of heterozygosity(LOH) at the LKB1 locus at 19p was seen in 14 other polyps. In adenomatous lesions microdessected from hamartomatous polyps, both β-catenin mutation and 19p LOH were detected. Furthermore, a carcinomatous lesion in a gastric hamartomatous polyp was found to contain a mutation of the p53 gene and LOH at the p53 locus in addition to LOR at the LKB1 locus and a β-catenin mutaion. K-ras mutations were detected in a few polyps, whereas no.APC mutation or 5g LOH was detected in hamartomatous polyps. 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 β-catenin gene and p53 genes convert hamrtomatous polyps into adenomatous and carcinomatous lesions.
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