Jpn J Cancer Res  1997 Sep;88(9):846-54 

Frequent somatic mutations of the APC and p53 genes in sporadic ampullary
carcinomas.

Imai Y, Oda H, Tsurutani N, Nakatsuru Y, Inoue T, Ishikawa T.

Department of Pathology, Faculty of Medicine, University of Tokyo.

Although a close relation of somatic mutations of the adenomatous polyposis coli
gene with ampullary carcinomas in familial adenomatous polyposis patients has
been reported, the possible association with sporadic ampullary neoplasms has
not been fully examined. We have therefore investigated loss of heterozygosity
at the adenomatous polyposis coli locus and the mutational status of a portion
of the adenomatous polyposis coli gene, including the mutation cluster region,
in 17 ampullary carcinomas of non-familial adenomatous polyposis patients.
Alteration of the adenomatous polyposis coli gene was found in 8 of 17 (47.1%)
cases, as missense or insertion mutations, with or without loss of
heterozygosity. Additional investigation of p53 (exons 5-8) and K-ras (codons 12
and 13) gene mutations revealed a striking mutational pattern of the p53 gene.
Nine of the 17 cases demonstrated a total of 12 mutations, 6 clustered at codon
189 and 3 at codon 166. Furthermore, 5 of the 12 mutations were nonsense
mutations. Regarding the K-ras gene, 4 of the 17 (23.5%) cases had mutations in
codon 12, 3 of the 4 cases being derived from the intraduodenal bile duct. The
findings indicate that alterations of the adenomatous polyposis coli and the p53
genes are relatively frequent in sporadic ampullary carcinomas. In particular,
the clustering at specific p53 codons might offer an etiological clue to clarify
ampullary carcinogenesis. Mutations of the K-ras gene, on the other hand, might
be characteristic of intraduodenal bile duct origin.

PMID: 9369932 [PubMed - indexed for MEDLINE]