MUTATIONS IN BETA-CATENIN ARE UNCOMMON IN COLORECTAL-CANCER OCCURRINGIN OCCASIONAL REPLICATION ERROR-POSITIVE TUMORS

beta-Catenin has been identified as an oncogene in colon cancer and me lanoma, Phosphorylation of sites in exon 3 of beta-catenin leads to de gradation of this protein. These sites are primary targets for activat ing mutations. The frequency with which oncogenic mutations at these s ites are found in colorectal cancer is unknown, as is the frequency of their occurrence in other malignancies, We analyzed 92 colorectal can cers (CRCs) and 57 cancer cell lines (representing a diversity of tumo r types) to determine the frequency of activating mutations in this ge ne, Mutations in exon 3 of beta-catenin were found in 2 of 92 CRCs and in the colorectal cancer cell line HCT 116. Both tumors with beta-cat enin mutations exhibited widespread microsatellite instability, which is indicative of a replication error phenotype, a phenotype known to b e present in HCT 116. This suggests that mutations in beta-catenin are infrequent in CRC and miscellaneous cancer cell lines and may occur i n association with a replication error phenotype.