Abstract
Alterations of the APC, K-ras, and β-catenin genes are defined as early events in colorectal tumorigenesis. These alterations are well-known as constitutents of Vogelstein's pathway, however, the relationship among them is unclear. For understanding colorectal tumorigenesis it is important to evaluate their relationship. We analyzed the relationship between β-catenin and K-ras gene mutations in clinical colorectal samples. Sixty-four cases of colorectal cancers (44 proximal, 20 distal) without a family history of colorectal cancer were used for this study. We purified genomic DNAs from fresh surgical samples and, thus, analyzed the mutations of β-catenin (exon 3) and K-ras (codons 12 and 13) by PCR direct sequencing method using Big Dye terminator cycle sequencing with AmpliTaq polymerase FS. We found 27% (17/64) K-ras mutations (proximal 25%, 11/44; distal 30%, 6/20). The frequency of β-catenin mutations was 11% (7/64; proximal 9%, 4/44; distal 15%, 3/20). All cases with β-catenin mutation had no mutation of K-ras. All sites of β-catenin mutation have been reported previously (codons 33, 34, 41, 45). In cell lines, it has been reported previously that β-catenin and K-ras play the same roles in activation of cyclin D1 transcription. Our results may support this report and suggest that some colorectal cancers with β-catenin mutation will progress without K-ras mutation. Further study may disclose a new pathway or new mechanism of colorectal tumorigenesis.
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Shitoh, K., Koinuma, K., Furukawa, T. et al. Mutation of β-Catenin Does Not Coexist with K-ras Mutation in Colorectal Tumorigenesis. Dig Dis Sci 49, 1631–1633 (2004). https://doi.org/10.1023/B:DDAS.0000043376.41820.a6
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DOI: https://doi.org/10.1023/B:DDAS.0000043376.41820.a6