The APC/beta-catenin pathway in ulcerative colitis-related colorectal carcinomas: a mutational analysis.
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.
Aust
Daniela E
DE
Pathologisches Institut der Ludwig-Maximilians-Universität, München, Germany.
Terdiman
Jonathan P
JP
Willenbucher
Robert F
RF
Chang
Cornell G
CG
Molinaro-Clark
Annette
A
Baretton
Gustavo B
GB
Loehrs
Udo
U
Waldman
Frederic M
FM
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005091:Exons; D005260:Female; D007839:Functional Laterality; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D015534:Trans-Activators; D051176:beta Catenin