[Promoter hypermethylation and loss of heterozygosity of the APC gene in patients with familial adenomatous polyposis].

OBJECTIVE: To investigate the status of hypermethylation in the promoter 1A region of the adenomatus polyposis coli (APC) gene in 3 familial adenomatous polyposis (FAP) pedigrees and to screen large fragment deletions in the APC gene. METHODS: DNA from tumor tissues and corresponding normal tissues of 5 FAP patients was modified by sodium bisulfite. Then the methylation status of the APC gene was analyzed by methylation specific-PCR (MSP) and DNA sequencing. Multiplex ligation-dependent probe amplification (MLPA) was used to screen aberrations involving large fragments from all the 15 exons and promoter region of APC gene. RESULTS: No methylation was present in normal tissues. Hypermethylation was found in tumor tissues of one proband and her son. Loss of heterozygosity was observed in another patient from the same FAP family. CONCLUSION: Aberrant methylation of the APC promoter region provides an important mechanism for impairing APC function and may occur early during colon neoplasia progression. Loss of heterozygosity may play a role in patients with classical polyposis.