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The APC/β-catenin pathway in ulcerative colitis–related colorectal carcinomas
A mutational analysis
Version of Record online: 11 MAR 2002
Copyright © 2002 American Cancer Society
Volume 94, Issue 5, pages 1421–1427, 1 March 2002
How to Cite
Aust, D. E., Terdiman, J. P., Willenbucher, R. F., Chang, C. G., Molinaro-Clark, A., Baretton, G. B., Loehrs, U. and Waldman, F. M. (2002), The APC/β-catenin pathway in ulcerative colitis–related colorectal carcinomas. Cancer, 94: 1421–1427. doi: 10.1002/cncr.10334
- Issue online: 11 MAR 2002
- Version of Record online: 11 MAR 2002
- Manuscript Accepted: 7 NOV 2001
- Manuscript Received: 2 OCT 2001
- NIH. Grant Number: CA-74826
- Deutsche Forschungsgemeinschaft Au. Grant Number: 141/1-1
- adenomatous polyposis coli (APC);
- ulcerative colitis;
- colorectal carcinoma
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.
The mutational cluster region of APC (codon 1267 to 1529) and exon 3 of the β-catenin were directly sequenced.
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.
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.