Beta-catenin mutations in hepatocellular carcinoma correlate with a low rate of loss of heterozygosity

Oncogene. 1999 Jul 8;18(27):4044-6. doi: 10.1038/sj.onc.1202800.

Abstract

To determine the frequency of Wnt/Wingless beta catenin pathway alteration in human hepatocellular carcinoma, a beta catenin and APC gene mutation screening was performed in a series of 119 tumors. An activating beta catenin mutation in exon 3 was found in 18% of the cases. Among tumors lacking beta catenin mutation, no APC mutation has been evidenced in a subset of 30 cases tested. The correlation between beta catenin mutation status and chromosome segment deletions was studied on a set of 48 hyperploid tumors. Chromosome 1p, 4q and 16p deletions were significantly associated with the absence of beta catenin mutation (P<0.05). Furthermore the Fractional Allelic Loss was significantly smaller in the beta catenin mutated tumors than in the non-mutated tumors (0.12 versus 022). Taken together, these results suggest, the existence of two carcinogenesis mechanisms. The first mechanism implies a beta catenin activating mutation associated with a low rate of loss of heterozygosity. The second mechanism, operating in a context of chromosomal instability, would involve tumor suppressor genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy
  • Cadherins / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Cytoskeletal Proteins / genetics*
  • DNA Mutational Analysis
  • Drosophila Proteins*
  • Genes, APC
  • Humans
  • Liver Neoplasms / genetics*
  • Loss of Heterozygosity*
  • Mutation*
  • Proto-Oncogene Proteins / genetics
  • Trans-Activators*
  • Wnt Proteins
  • Wnt1 Protein
  • Zebrafish Proteins*
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Drosophila Proteins
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Wnt Proteins
  • Wnt1 Protein
  • Zebrafish Proteins
  • beta Catenin
  • wg protein, Drosophila