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

Publisher Website
Google Scholar
Abstract
To determine the frequency of Wnt/Wingless β catenin pathway alteration in human hepatocellular carcinoma, a β catenin and APC gene mutation screening was performed in a series of 119 tumors. An activating β catenin mutation in exon 3 was found in 18% of the cases. Among tumors lacking β catenin mutation, no APC mutation has been evidenced in a subset of 30 cases tested. The correlation between β 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 β catenin mutation (P<0.05). Furthermore the Fractional Allelic Loss was significantly smaller in the β 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 β 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.