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

Andrew B. Sparks, Patrice J. Morin, Bert Vogelstein, Kenneth W. Kinzler

Research output: Contribution to journalArticlepeer-review

870 Scopus citations


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 β-catenin/Tcf-mediated transcription. To further explore the role of the APC/β-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 γ-catenin (CTNNG1), GSK-3α (GSK3A), or GSK-3β (GSK3B) genes were detected. In contrast, mutations in the NH2-terminal regulatory domain of β-catenin (CTNNB1) were found in 13 of 27 (48%) CR tumors lacking APC mutations. Mutations in the β-catenin regulatory domain and APC were observed to be mutually exclusive, consistent with their equivalent effects on β-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 β-catenin signaling plays a critical role in CR tumorigenesis.

Original languageEnglish (US)
Pages (from-to)1130-1134
Number of pages5
JournalCancer Research
Issue number6
StatePublished - Mar 15 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Mutational analysis of the APC/β-catenin/Tcf pathway in colorectal cancer'. Together they form a unique fingerprint.

Cite this