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

To determine the frequency of Wnt/Wingless beta catenin pathway alteration in human hepatocellular carcinoma, a beta catenin and APC gene mutation scr eening 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 cas es tested. The correlation between beta catenin mutation status and chromos ome segment deletions was studied on a set of 48 hyperploid tumors. Chromos ome 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 n on-mutated tumors (0.12 versus 022), Taken together, these results suggest, the existence of two carcinogenesis mechanisms, The first mechanism implie s 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.