beta-catenin mutations are more frequent in small colorectal adenomas thanin larger adenomas and invasive carcinomas

Loss of serine or threonine phosphorylation sites from exon 3 of beta-caten in has been identified in approximately half of colorectal tumors which lac k adenomatous polyposis coli (AFC) mutations, but the overall contribution of beta-catenin mutations to sporadic colorectal tumorigenesis is unclear. We therefore used PCR to amplify and sequence exon 3 of beta-catenin from 2 02 sporadic colorectal tumors. Exon 3 beta-catenin mutations were identifie d in 6 of 48 small (<1 cm) adenomas, 2 of 82 large (greater than or equal t o 1 cm) adenomas, and 1 of 72 invasive carcinomas. Eight of the nine mutati ons, including all of those in the small adenomas and the invasive cancer, involved loss of serine or threonine phosphorylation sites. The percentage of beta-catenin mutations in small adenomas (12.5%) was significantly great er than that in large adenomas (2.4%) and invasive cancers (1.4%; P = 0.05 and P = 0.02, respectively). We conclude that mutation of beta-catenin can be an early, perhaps initiating, event in colorectal tumorigenesis. Small a denomas with beta-catenin mutations do not appear to be as likely to progre ss to larger adenomas and invasive carcinomas as other adenomas, however, w ith the result that beta-catenin mutations are only rarely seen in invasive cancers, This suggests that APC and beta-catenin mutations are not functio nally equivalent, and that the APC gene may have other tumor suppressor fun ctions besides the degradation of beta-catenin.