Childhood hepatocellular adenoma in familial adenomatous polyposis: Mutations in adenomatous polyposis coli gene and p53

Background & Aims: Infantile and childhood liver tumors have been found in 0.42% of individuals with a germline mutation in the adenomatous polyposis coli (APC) gene. This study analyzed a hepatocellular adenoma of a 2-year-old child at risk for familial adenomatous polyposis to identify genetic alterations in hepatic tumors initiated by APC germline mutations. Methods: Mutation screening was performed for the APC gene (protein truncation test and DNA sequence analysis), p53 gene (complementary DNA cloning and sequencing), and members of the Ras gene family (complementary DNA sequence analysis). Results: Both the mother and child had a germinal CGA --> TGA transition at codon 1451 leading to an Arg14517ev stop mutation in the APC gene. Loss of the wild-type APC allele as a second hit revealed hemizygosity of the inherited mutation in the tumor. Furthermore, a CGC --> CAC transition in the p53 gene of the adenoma resulted in an Arg --> His missense mutation in codon 175. No loss of heterozygosity was detected at the p53 locus. Res gene mutations weve not found. Conclusions: Biallelic inactivation of APC gene and p53 mutation ave early events in hepatocellular tumorigenesis. Additional reports will confirm whether inherited APC gene mutations between codon 1444 and 1578 increase the risk for hepatic tumors.