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 journalArticle

Abstract

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
Volume58
Issue number6
StatePublished - Mar 15 1998

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Catenins
Adenomatous Polyposis Coli
Colorectal Neoplasms
Mutation
Glycogen Synthase Kinase 3
Carcinogenesis
Tumor Suppressor Genes
Transcriptional Activation
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mutational analysis of the APC/β-catenin/Tcf pathway in colorectal cancer. / Sparks, Andrew B.; Morin, Patrice J.; Vogelstein, Bert; Kinzler, Kenneth W.

In: Cancer Research, Vol. 58, No. 6, 15.03.1998, p. 1130-1134.

Research output: Contribution to journalArticle

Sparks, Andrew B. ; Morin, Patrice J. ; Vogelstein, Bert ; Kinzler, Kenneth W. / Mutational analysis of the APC/β-catenin/Tcf pathway in colorectal cancer. In: Cancer Research. 1998 ; Vol. 58, No. 6. pp. 1130-1134.
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