RAS-FAMILY GENE-MUTATIONS IN NEOPLASIA OF THE AMPULLA OF VATER

Mutations in the first and second exons of Ha-, Ki- and N-ras oncogene s were investigated in 17 epithelial tumors of the ampulla of Vater by single-strand conformation polymorphism analysis and direct sequencin g of DNA fragments amplified by polymerase chain reaction. The panel i ncluded 12 intestinal-type adenocarcinomas, 3 villous adenomas, 1 papi llary carcinoma and 1 neuroendocrine carcinoma. Six cases (35%) contai ned ras mutations, affecting codon 12 of Ki-ras in 2 adenomas and 3 ca rcinomas, and of N-ras in 1 adenoma. All mutations were found in adeno mas and among cancers with adenomatous areas, whereas non of the cases lacking adenomatous areas contained mutations. This suggested that am pullary cancer represent heterogeneous diseases with respect to the pr esence or absence of adenomatous areas and, among those with adenomato us areas, with respect to the presence of activated ras genes. Ki-ras mutated cases included 3 of 4 tumors which mainly involved the intradu odenal bile duct, thus suggesting that a proportion of Ki-ras -mutated ampullary cancers might correspond to those originating from the epit helium of the bile duct component of the ampulla. (C) 1994 Wiley-Liss, Inc.