Novelty of Axin 2 and lack of Axin 1 gene mutation in colorectal cancer: a study in Kashmiri population
Novelty of Axin 2 and lack of Axin 1 gene mutation in colorectal cancer: a study in Kashmiri population
复制标题
DOI：
10.1007/s11010-011-0848-8
复制
发表时间：
2011-09-01
影响因子：
4.3
通讯作者：
Mudassar, Syed
中科院分区：
文献类型：
--
作者：
Khan, Nighat P.;Pandith, Arshad A.;Mudassar, Syed
结直肠癌（CRC）是死亡率和发病率的主要原因之一。多种遗传因素已被报道参与结直肠癌的发展，包括Axin基因。Axin是一种重要的支架蛋白，在多种生物信号转导途径中发挥重要作用。我们的目的是研究克什米尔人结直肠癌患者Axin基因的突变模式。我们的研究中使用了50例连续CRC患者的成对肿瘤和相邻正常组织标本。通过直接DNA测序评价DNA制备物中Axin 1和Axin 2基因突变的发生。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。本研究在Axin 2基因第7外显子密码子G695 T（p丙氨酸>丝氨酸）处发现了一种新的G > T（GCT > TCT）颠换突变，频率为6%（3/50）。在Axin 2基因的同一外显子中，在密码子L 688 L（CCT > CTT）处检测到一个单核苷酸多态性（SNP），频率为36%（18/50）。Axin 1c外显子D 726 D（GAT > GAC）的SNP频率为62.5%（31/50）。这两个SNP是同义的，因此不会导致氨基酸的改变。虽然Axin 1和Axin 2基因突变已被发现与结直肠癌的发生有关，但在克什米尔人群中似乎相对罕见。然而，这项研究的一个有趣的发现是Axin 2基因突变的新奇，这可能是克什米尔种族人群中CRC的易感因素。
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.