As a signaling
protein in the Wnt pathway
beta-catenin plays a crucial role in the regulation of cellular proliferation. Recently, oncogenic
beta-catenin mutations were described in human
colorectal cancer and
melanoma cell lines. Since activating mutations in the
beta-catenin gene have similar effects on the biochemical level as inactivating mutations in the tumor suppressor gene APC, it is speculated that
beta-catenin mutations may substitute APC gene inactivation in
carcinogenesis. To address this question we analyzed twenty-three sporadic
colorectal tumors of different progression states for mutations in the
beta-catenin gene. Eighteen of these
tumors showed the wildtype APC gene sequence. In only one of the
tumors with wildtype APC a
beta-catenin gene mutation was found. This
tumor was of the RER (
replication error) phenotype which may explain the finding that the mutation occurred in a sequential repeat motif of the
beta-catenin gene. The second aim of this study was to investigate whether differences in the phenotypic variability in FAP (
familial adenomatous polyposis coli) might be due to inherited alterations in the
beta-catenin gene. For this we analyzed
DNA from fourteen FAP patients from eight different families for germline mutations in the
beta-catenin gene. We did not find any
beta-catenin gene alteration in these samples. Our results indicate that somatic
beta-catenin activating mutations contribute only to a minor part of human
colorectal tumors and that germline
beta-catenin mutations do not play a role in the variability of symptoms in FAP.