Cancer Res  1998 Mar 15;58(6):1130-4 

Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer.

Sparks AB, Morin PJ, Vogelstein B, Kinzler KW.

Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.

Mutation of the adenomatous polyposis coli (APC) tumor suppressor gene initiates
the majority of colorectal (CR) cancers. One consequence of this inactivation is
constitutive activation of beta-catenin/Tcf-mediated transcription. To further
explore the role of the APC/beta-catenin/Tcf pathway in CR tumorigenesis, we
searched for mutations in genes implicated in this pathway in CR tumors lacking
APC mutations. No mutations of the gamma-catenin (CTNNG1), GSK-3alpha (GSK3A),
or GSK-3beta (GSK3B) genes were detected. In contrast, mutations in the
NH2-terminal regulatory domain of beta-catenin (CTNNB1) were found in 13 of 27
(48%) CR tumors lacking APC mutations. Mutations in the beta-catenin regulatory
domain and APC were observed to be mutually exclusive, consistent with their
equivalent effects on beta-catenin stability and Tcf transactivation. In
addition, we found that CTNNB1 mutations can occur in the early, adenomatous
stage of CR neoplasia, as has been observed previously with APC mutations. These
results suggest that CTNNB1 mutations can uniquely substitute for APC mutations
in CR tumors and that beta-catenin signaling plays a critical role in CR
tumorigenesis.

PMID: 9515795 [PubMed - indexed for MEDLINE]