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

Abstract

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. The mutational cluster region of APC (codon 1267 to 1529) and exon 3 of the beta-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 beta-catenin mutation. 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.