Biallelic inactivation of the APC gene is associated with hepatocellular carcinoma in familial adenomatous polyposis coli

Cancer. 2001 Jul 15;92(2):332-9. doi: 10.1002/1097-0142(20010715)92:2<332::aid-cncr1327>3.0.co;2-3.

Abstract

Background: Certain primary hepatic tumors have been associated with familial adenomatous polyposis (FAP), a condition caused by germline mutations of the adenomatous polyposis coli (APC) gene. However, a genetic association between FAP and hepatocellular carcinoma (HCC) has not been shown. This study tested the hypothesis that biallelic inactivation of the APC gene contributed to the development of HCC in a patient with FAP and a known germline mutation of the APC gene at codon 208, but no other risk factors for HCC.

Methods: Total RNA and genomic DNA were isolated from the tumor, and in vitro synthesized protein assay and DNA sequencing analysis were used to screen for a somatic mutation in the APC gene.

Results: A somatic one-base pair deletion at codon 568 was identified in the wild-type allele of the APC gene.

Conclusions: To the authors' knowledge, this study provides the first evidence that biallelic inactivation of the APC gene may contribute to the development of HCC in patients with FAP.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenomatous Polyposis Coli / complications
  • Adenomatous Polyposis Coli / genetics*
  • Adult
  • Base Sequence
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • DNA Mutational Analysis
  • DNA, Neoplasm / analysis*
  • DNA, Neoplasm / genetics
  • Genes, APC / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Loss of Heterozygosity*
  • Male
  • Molecular Sequence Data
  • Risk Factors

Substances

  • DNA, Neoplasm