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Keywords:

  • adenomatous polyposis coli (APC);
  • β-catenin;
  • ulcerative colitis;
  • colorectal carcinoma

Abstract

BACKGROUND

Although the APC/β-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-/β-catenin pathway in UC-related carcinogenesis, the authors identified APC and β-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 β-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 β-catenin mutation.

CONCLUSIONS

Mutations of the APC and β-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/β-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. Cancer 2002;94:1421–7. © 2002 American Cancer Society.

DOI 10.1002/cncr.10334