APC gene mutations and allelic losses in sporadic ampullary tumours: Evidence of genetic difference from tumours associated with familial adenomatous polyposis

• Published in: International journal of cancer Vol. 68; no. 3; pp. 305 - 312
• Main Authors: Achille, Alberto, Scupoli, Maria T., Magalini, Alba R., Zamboni, Giuseppe, Romanelli, Maria G., Orlandini, Simonetta, Biasi, Maria O., Lemoine, Nicholas R., Accolla, Roberto S., Scarpa, Aldo
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 04-11-1996; Wiley-Liss
• Subjects: Adenomatous Polyposis Coli - complications; Adenomatous Polyposis Coli - genetics; Adult; Aged; Alleles; Ampulla of Vater; Biological and medical sciences; Chromosomes, Human, Pair 5; Common Bile Duct Neoplasms - complications; Common Bile Duct Neoplasms - genetics; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Deletion; Gene Expression Regulation, Neoplastic; Genes, APC; Genes, p53; Genes, ras; Heterozygote; Humans; Male; Medical sciences; Middle Aged; Mutation; Polymerase Chain Reaction; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Adenocarcinoma; Human; Carcinoma; Duodenal disease; Long arm; Heterozygosity loss; Malignant tumor; Adenoma; Chromosome B5; Vater ampulla; Carcinogenesis; TP53 Gene; Gene; C-Onc gene; Cytogenetics; Digestive diseases; Intestinal disease; Benign neoplasm; Mutation; Molecular biology; Comparative study; Protooncogene; Tumor suppressor gene
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19961104)68:3<305::AID-IJC7>3.0.CO;2-5

We explored APC gene mutations and chromosome 5q21 allelic losses (5qLOH) in 18 neoplasms of the papilla of Vater, including 6 early‐stage tumours (3 adenomas, 3 carcinomas) and 12 advanced‐stage cancers. Eleven 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. Mutations in the Ki‐ras, N‐ras and p53 genes were also assessed. We found: 5qLOH in 8 of 16 cases (50%), including 1 adenoma, 3 early‐ and 4 advanced‐stage cancers; APC mutations in 2 adenomas and 1 advanced‐stage carcinoma; Ki‐ or N‐ras mutations in 3 adenomas and 3 advanced‐stage cancers; p53 mutations in 2 early‐stage and 7 advanced‐stage adenocarcinomas. Our results suggest that 5qLOH, APC mutations and ras mutations are 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 in familial adenomatous polyposis in the frequency (17% vs. 64%) as well as in the site of APC somatic mutations, suggesting a different molecular pathogenesis in the 2 conditions. © 1996 Wiley‐Liss, Inc.