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

Int J Cancer. 1996 Nov 4;68(3):305-12. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / complications
  • Adenomatous Polyposis Coli / genetics*
  • Adult
  • Aged
  • Alleles*
  • Ampulla of Vater*
  • Chromosomes, Human, Pair 5
  • Common Bile Duct Neoplasms / complications
  • Common Bile Duct Neoplasms / genetics*
  • Female
  • Gene Deletion*
  • Gene Expression Regulation, Neoplastic
  • Genes, APC*
  • Genes, p53
  • Genes, ras
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction