Analysis of beta-catenin alterations in colon tumors: a novel exon 3 mutation

Abstract

The great majority of colorectal cancers have defects in the Wnt signaling pathway indicating that this pathway has an important role in carcinogenesis. Alterations in the beta-catenin gene are observed in 10-50% of the patients with colorectal cancer. Mutations of the beta-catenin gene frequently occur in a region coding the protein phosphorylation domain harboring the Ser33/37/Thr41 and Ser45 sites and the inhibition of phosphorylation. Disruption of the beta-catenin regulation plays a critical role in tumor development. In this study, we analyzed expression and mutations of beta-catenin and phosphorylation of the Ser45 and Ser33/37/Thr41 residues in the tumors and matched normal tissue samples of patients with colorectal cancer. We did not observe significant differences in the phosphorylation rates between the patients and the control group. Samples displaying different levels of phosphorylation in the tumor and normal tissue were analyzed for exon 3 mutations of the beta-catenin gene. In three of 57 patients, a novel G to A substitution was found at codon 15. This nucleotide change has not been reported previously in the literature. beta-catenin protein levels and the degree of Ser45 or Ser33/37/Thr41 phosphorylation in tumor and normal tissue were not associated with the clinical parameters. Our results indicate that differences in the expression and phosphorylation of beta-catenin are not very frequent in colon cancer, but mutations in exon 3 of the beta-catenin gene may be responsible for a significant proportion of the tumors.