Cancer Res  1999 Apr 1;59(7):1442-4 

Beta-catenin mutations are more frequent in small colorectal adenomas than in
larger adenomas and invasive carcinomas.

Samowitz WS, Powers MD, Spirio LN, Nollet F, van Roy F, Slattery ML.

Department of Pathology, University of Utah Health Sciences Center, Salt Lake
City 84132, USA.

Loss of serine or threonine phosphorylation sites from exon 3 of beta-catenin
has been identified in approximately half of colorectal tumors which lack
adenomatous polyposis coli (APC) 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 202
sporadic colorectal tumors. Exon 3 beta-catenin mutations were identified in 6
of 48 small (< 1 cm) adenomas, 2 of 82 large (> or =1 cm) adenomas, and 1 of 72
invasive carcinomas. Eight of the nine mutations, 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 greater 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 adenomas with beta-catenin mutations do not
appear to be as likely to progress to larger adenomas and invasive carcinomas as
other adenomas, however, with the result that beta-catenin mutations are only
rarely seen in invasive cancers. This suggests that APC and beta-catenin
mutations are not functionally equivalent, and that the APC gene may have other
tumor suppressor functions besides the degradation of beta-catenin.

PMID: 10197610 [PubMed - indexed for MEDLINE]