beta-catenin mutation and expression analysis in ovarian cancer: exon 3 mutations and nuclear translocation in 16% of endometrioid tumours

Int J Cancer. 1999 Aug 27;82(5):625-9. doi: 10.1002/(sici)1097-0215(19990827)82:5<625::aid-ijc1>;2-2.


The molecular mechanisms involved in the generation of epithelial ovarian cancers are poorly understood, but evidence suggests that the different histological subtypes may arise from independent tumorigenic events. beta-Catenin is emerging as an important oncogene in the transformation of a number of epithelial cancers, and mutations have been reported in a small study of endometrioid ovarian adenocarcinomas. Mutations in the NH(2)-regulatory domain of beta-catenin stabilise the cytoplasmic levels of this protein, which promotes up-regulation of the beta-catenin-T-cell factor-lymphoid enhancer factor transcriptional complex. We report here beta-catenin (CTNNB1) exon 3 mutation analysis in 149 epithelial ovarian carcinomas. This revealed 10/63 (16%) endometrioid ovarian tumours with activating mutations of the beta-catenin gene. All mutations were missense changes within the GSK3beta consensus site, affecting serine residues at codons 33 and 37 and glycine at codon 34. Immuno-histochemical analysis identified cytoplasmic stabilisation and nuclear translocation in those endometrioid tumours with mutations. This phenotypic change was also identified in 3 other endometrioid tumours that did not have somatic mutations within exon 3 of CTNNB1. Stabilisation of the free, monomeric pool of beta-catenin and the probable resulting constitutive activation of its Tcf-associated transcriptional complex appears to be a specific oncogenic event in endometrioid ovarian adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Cell Nucleus / physiology
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / genetics*
  • DNA Mutational Analysis
  • Disease Progression
  • Exons
  • Female
  • Gene Rearrangement
  • Humans
  • Immunohistochemistry
  • Mutation*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Trans-Activators*
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin