The APC/beta-catenin pathway in ulcerative colitis-related colorectal carcinomas: a mutational analysis

Cancer. 2002 Mar 1;94(5):1421-7. doi: 10.1002/cncr.10334.


Background: Although the APC/beta-catenin pathway is known to play a crucial role in sporadic colorectal carcinogenesis, its influence on ulcerative colitis (UC)-related neoplastic progression is unknown. To elucidate the role of the APC-/beta-catenin pathway in UC-related carcinogenesis, the authors identified APC and beta-catenin mutations in a set of UC-related and sporadic colorectal carcinomas.

Methods: The mutational cluster region of APC (codon 1267 to 1529) and exon 3 of the beta-catenin were directly sequenced.

Results: Only 1 of 30 UC-related tumors (3%) showed an APC mutation whereas 11 of the 42 sporadic carcinomas (26%) had mutations within the mutational cluster region. Within the sporadic carcinoma group, only 8% of the right-sided carcinomas showed APC mutations whereas 50% of the left-sided carcinomas had mutations within the mutational cluster region. None of the tumors in either group showed a beta-catenin mutation.

Conclusions: Mutations of the APC and beta-catenin are rare in UC-related tumors. These genes may be altered because of mutations outside the regions studied, or by epigenetic silencing. Alternatively, other proteins involved in the APC/beta-catenin signaling cascade may be altered, or this pathway may be involved infrequently in UC-related carcinogenesis. The significant difference in frequency of APC mutations between right- and left-sided sporadic tumors suggests different molecular pathways in these two tumor sites.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics*
  • Adult
  • Aged
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Transformation, Neoplastic*
  • Colitis, Ulcerative / genetics*
  • Colitis, Ulcerative / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Cytoskeletal Proteins / genetics*
  • DNA Mutational Analysis
  • DNA Primers
  • Exons
  • Female
  • Functional Laterality
  • Humans
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Signal Transduction
  • Trans-Activators*
  • beta Catenin


  • Adenomatous Polyposis Coli Protein
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA Primers
  • Trans-Activators
  • beta Catenin