We screened for genetic alterations of adenomatous polyposis coli (APC) and β-catenin genes in 17 frozen specimens from 12 cases of sporadic desmoid tumors and then subdivided these cases into two groups according to the results of mutational analysis. We further examined mRNA expression of β-catenin and cyclin D1 by TaqMan PCR and compared the mRNA expression within both groups. Single-strand conformation polymorphism analysis followed by DNA direct sequencing revealed β-catenin mutation in 3 of 12 cases (6 of 17 specimens), whereas no APC missense mutations in the mutation cluster region were found. TaqMan PCR revealed extremely higher mRNA expression of β-catenin and cyclin D1 in desmoid tumors, compared with those of normal skeletal muscles. In the β-catenin mutated group, cyclin D1 mRNA expression was significantly higher than that of the β-catenin wild-type group (p = 0.0120, Mann-Whitney U test). In addition, in the β-catenin mutated group, β-catenin mRNA expression was also significantly higher than that of the β-catenin wild-type group (p = 0.0036, Mann-Whitney U test). All cases of desmoid tumors showed detectable β-catenin nuclear expression immunohistochemically. These results suggest that a continuously elevated β-catenin protein level caused by the β-catenin mutation itself may have a stronger power that can transactivate transcription in vivo. Furthermore, the results provide a possible association between higher β-catenin mRNA expression and mutated β-catenin in sporadic desmoid tumors. This may suggest that the β-catenin gene may be up-regulated by mutated or continuously elevated β-catenin protein, that is, the β-catenin gene may also be one of the targeted genes in the APC-β-catenin-Tcf pathway.
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