535 Background: Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary colorectal tumor syndrome characterized by the formation of a number of adenomatous polyps throughout the entire colon. Clinically, a precise family history together with surveillance of the colon as well as extra-colonic organs for people at risk is important to prevent cancer progression because of an almost 100% lifetime risk of colorectal cancer if the colon is not removed. Although there are fascinating correlations between the location of the APC mutation and the clinical phenotype, none has reported about genotype-phenotype correlation of gastric cancer in FAP, which occupies 2.1-4.2% in East Asia. Methods: Peripheral blood samples were obtained from 29 probands that was clinically diagnosed with FAP and DNA was extracted from the peripheral blood. All the coding exons of APC and their boundary regions were amplified using PCR and were directly sequenced. For large deletion/insertion analysis, an MLPA was performed using MLPA kit (P043 APC, MRC-Holland). Using results from the APC mutation analysis, we examined correlation between location of APCgermline mutation and clinical phenotype including gastric cancer. Results: Among 16 probands (3 cases were severe FAP, 12 cases classical FAP, and one case attenuated FAP) that were identified APC germline mutation, correlation between density of colonic adenomatous polypsosis and distribution of the APC mutation donated the same tendency of previous report. Among the 16 probands, 11 had fundic gland polyposis (FGPs) of the stomach and three had gastric adenocarcinoma (one case with FGPs and others without FGPs). Interestingly, all the three cases did not have severe adenomatous polyposis of the colon and their APC mutations were distributed at the location that is reported to be correlated with attenuated FAP. Conclusions: Patients with gastric cancer in FAP clinically have a tendency of having non-severe adenomatous polyposis of the colon and their location of APC mutation may be correlated to the hot spot location of attenuated FAP, suggesting that patient with non-severe colonic adenomatous polyp should have upper GI screening for gastric cancer prevention.
High-grade dysplasia associated with fundic gland polyposis in a familial adenomatous polyposis patient, with special reference to APC mutation profiles
