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The APC/β‐catenin pathway in ulcerative colitis–related colorectal carcinomas
Author(s) -
Aust Daniela E.,
Terdiman Jonathan P.,
Willenbucher Robert F.,
Chang Cornell G.,
MolinaroClark Annette,
Baretton Gustavo B.,
Loehrs Udo,
Waldman Frederic M.
Publication year - 2002
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.10334
Subject(s) - carcinogenesis , cancer research , catenin , beta catenin , mutation , ulcerative colitis , medicine , adenomatous polyposis coli , exon , colorectal cancer , biology , cancer , gene , wnt signaling pathway , pathology , genetics , disease
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