Mutation of beta-catenin does not coexist with K-ras mutation in colorectal tumorigenesis.
Alterations of the APC, K-ras, and beta-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 beta-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 beta-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 beta-catenin mutations was 11% (7/64; proximal 9%, 4/44; distal 15%, 3/20). All cases with beta-catenin mutation had no mutation of K-ras. All sites of beta-catenin mutation have been reported previously (codons 33, 34, 41, 45). In cell lines, it has been reported previously that beta-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 beta-catenin mutation will progress without K-ras mutation. Further study may disclose a new pathway or new mechanism of colorectal tumorigenesis.
Shitoh
Kazuhisa
K
Department of Surgery, Jichi Medical School, Tochigi-ken, Japan. kshitoh@jichi.ac.jp
Koinuma
Koji
K
Furukawa
Taiji
T
Okada
Masaki
M
Nagai
Hideo
H
D015179:Colorectal Neoplasms / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D009154:Mutation; D015534:Trans-Activators / Q000235:genetics*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D015534:Trans-Activators; D051176:beta Catenin