APC GENE-MUTATIONS AND ALLELIC LOSSES IN SPORADIC AMPULLARY TUMORS - EVIDENCE OF GENETIC DIFFERENCE FROM TUMORS ASSOCIATED WITH FAMILIAL ADENOMATOUS POLYPOSIS

We explored APC gene mutations and chromosome 5q21 allelic losses (5qL OH) in 18 neoplasms of the papilla of Vater, including 6 early-stage t umours (3 adenomas, 3 carcinomas) and IZ advanced-stage cancers. Eleve n PCR-amplified polymorphic sequences were used to analyse 5qLOH. APC mutations were investigated both by an in vitro APC-protein truncation test and by single-strand conformation polymorphism analysis. Mutatio ns in the Ki-ras, N-ras and p53 genes were also assessed. We found: 5q LOH in 8 of 16 cases (50%), including 1 adenoma, 3 early- and 4 advanc ed-stage cancers; APC mutations in 2 adenomas and 7 advanced-stage car cinoma; Ki- or N-ras mutations in 3 adenomas and 3 advanced-stage canc ers; p53 mutations in 2 early-stage and 7 advanced-stage adenocarcinom as. Our results suggest that 5qLOH, APC mutations and ras mutations ar e present at early stages, whereas p53 inactivation is associated with progression of malignancy in a large proportion of cases. These data indicate that sporadic ampullary tumours differ from those occurring i n familial adenomatous polyposis in the frequency (17% vs. 64%) as wel l as in the site of APC somatic mutations, suggesting a different mole cular pathogenesis in the 2 conditions. (C) 1996 Wiley-Liss, Inc.