Mutation of β-catenin does not coexist with K-ras mutation in colorectal tumorigenesis
Mutation of β-catenin does not coexist with K-ras mutation in colorectal tumorigenesis
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DOI：
10.1023/b:ddas.0000043376.41820.a6
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发表时间：
2004-10-01
影响因子：
3.1
通讯作者：
Nagai, H
中科院分区：
文献类型：
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作者：
Shitoh, K;Koinuma, K;Nagai, H
APC、K-ras和β-连环蛋白基因的改变被定义为结直肠肿瘤发生的早期事件。这些改变是众所周知的Vogelstein途径的组成部分，然而，它们之间的关系尚不清楚。为了了解结直肠肿瘤的发生，重要的是要评估它们之间的关系。我们分析了临床结直肠标本中β-catenin和K-ras基因突变的关系。64例无结直肠癌家族史的结直肠癌（近端44例，远端20例）用于本研究。我们从新鲜手术样本中纯化基因组DNA，并通过PCR直接测序法使用AmpliTaq聚合酶FS进行Big Dye终止子循环测序，分析β-catenin（外显子3）和K-ras（密码子12和13）的突变。我们发现27%（17/64）的K-ras突变（近端25%，11/44;远端30%，6/20）。β-连环蛋白突变的频率为11%（7/64;近端9%，4/44;远端15%，3/20）。所有β-catenin突变病例均无K-ras突变。先前已经报道了β-连环蛋白突变的所有位点（密码子33、34、41、45）。在细胞系中，先前已经报道β-连环蛋白和K-ras在细胞周期蛋白D1转录的激活中发挥相同的作用。我们的研究结果可能支持这一报告，并建议一些大肠癌与β-catenin突变将进展没有K-ras突变。进一步的研究可能揭示大肠肿瘤发生的新途径或新机制。
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.