β-Catenin mutation and expression analysis in ovarian cancer: Exon 3 mutations and nuclear translocation in 16% of endometrioid tumours
✍ Scribed by Kim Wright; Peter Wilson; Sarah Morland; Ian Campbell; Michael Walsh; Terry Hurst; Bruce Ward; Margaret Cummings; Georgia Chenevix-Trench
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 134 KB
- Volume
- 82
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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. -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 -catenin stabilise the cytoplasmic levels of this protein, which promotes up-regulation of the -catenin-T-cell factor-lymphoid enhancer factor transcriptional complex. We report here -catenin (CTNNB1) exon 3 mutation analysis in 149 epithelial ovarian carcinomas. This revealed 10/63 (16%) endometrioid ovarian tumours with activating mutations of the -catenin gene. All mutations were missense changes within the GSK3 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 -catenin and the probable resulting constitutive activation of its Tcf-associated transcriptional complex appears to be a specific oncogenic event in endometrioid ovarian adenocarcinoma.