Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Srinagar 190 011, Kashmir, India.
Mol Cell Biochem. 2011 Sep;355(1-2):149-55. doi: 10.1007/s11010-011-0848-8. Epub 2011 May 4.
Colorectal cancer is (CRC) one of the leading causes of mortality and morbidity. Various genetic factors have been reported to be involved in the development of colorectal cancers including Axin gene. Axin, a major scaffold protein, plays an important role in various bio signaling pathways. We aim to study mutational pattern of Axin gene in colorectal cancer patients of Kashmiri population. The paired tumor and adjacent normal tissue specimens of 50 consecutive patients with CRC were used in our study. The DNA preparations were evaluated for the occurrence of Axin 1 and Axin 2 gene mutations by direct DNA sequencing. We analyzed exon 1a, 1b, 1c, 2, 4, 6, and 10 of Axin 1 and exon 7 of Axin 2. In this study, we found a novel mutation of G>T (GCT>TCT) transversion in exon 7 of Axin 2 gene at codon G695T (p.alanine > serine) at a frequency of 6% (3/50). In the same exon of Axin 2 gene a single nucleotide polymorphism (SNP) was detected in codon L688L (CCT>CTT) at a frequency of 36% (18/50). In exon 1c of Axin 1 a SNP was detected at codon D726D (GAT>GAC) at a frequency of 62.5% (31/50). Both the SNPs were synonymous hence do not lead to change of amino acid. Although Axin 1 and Axin 2 gene mutations have been found to be involved in the development of colorectal cancers, it seems to be a relatively rare event in Kashmiri population. However, an interesting finding of this study is the novelty of Axin 2 gene mutations which may be a predisposing factor in ethnic Kashmiri population to CRC.
结直肠癌（CRC）是导致死亡率和发病率的主要原因之一。已经报道了各种遗传因素参与了结直肠癌的发展，包括 Axin 基因。Axin 是一种主要的支架蛋白，在各种生物信号通路中发挥重要作用。我们旨在研究克什米尔人群结直肠癌患者 Axin 基因的突变模式。我们的研究使用了 50 例连续 CRC 患者的配对肿瘤和相邻正常组织标本。通过直接 DNA 测序评估 DNA 制剂中 Axin 1 和 Axin 2 基因的突变发生情况。我们分析了 Axin 1 的外显子 1a、1b、1c、2、4、6 和 10 以及 Axin 2 的外显子 7。在这项研究中，我们发现 Axin 2 基因外显子 7 中的 G>T（GCT>TCT）颠换的新突变，在密码子 G695T（p.丙氨酸>丝氨酸）的频率为 6%（3/50）。在 Axin 2 基因的同一外显子中，在密码子 L688L（CCT>CTT）检测到单核苷酸多态性（SNP），频率为 36%（18/50）。在 Axin 1 的外显子 1c 中，在密码子 D726D（GAT>GAC）检测到 SNP，频率为 62.5%（31/50）。这两个 SNP 都是同义的，因此不会导致氨基酸的变化。尽管已经发现 Axin 1 和 Axin 2 基因的突变参与了结直肠癌的发展，但在克什米尔人群中似乎是一个相对罕见的事件。然而，这项研究的一个有趣发现是 Axin 2 基因突变的新颖性，这可能是克什米尔人群易患 CRC 的一个易感因素。
