Genetic mutations of p53 and k-ras in gastric carcinoma patients from Hunan, China
Genetic mutations of p53 and k-ras in gastric carcinoma patients from Hunan, China
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DOI：
10.1007/s13277-010-0129-2
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发表时间：
2011-04-01
期刊：
影响因子：
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通讯作者：
Zhang, Dian-zheng
中科院分区：
文献类型：
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作者：
Chen, Han-chun;Chen, Hui-juan;Zhang, Dian-zheng
本研究采用病例对照研究方法，对12 3例胃癌患者和12 9例湖南正常人中国的P53、k-ras基因突变进行了研究。通过提取外周血基因组DNA，采用聚合酶链式反应-单链构象多态性分析和DNA测序，检测p53外显子-5、6、7、8和k-ras的突变。P53基因总突变率为29.3%，4个外显子均有突变。点突变以G：C->；A：T最高(41.7%)，其次是A：T->；G：C(25%)，G：C->；C：G(11.1%)，G：C->；T：A(8.3%)，A：T->；T：A(2.8%)。移码突变为11.1%。外显子5的密码子131、132、133、135、149、151、162、167、173、174和175，外显子6的密码子-193、197、213和215，外显子7的密码子-245、246、248、249和270，以及p53外显子8的密码子-271、272、273和282发生突变。K-ras基因突变频率为9.8%，主要发生在密码子-12(91.7%)和密码子-13(8.3%)。P53与k-ras基因突变在胃癌患者中无明显相关性。P53基因突变与年龄、性别、吸烟或饮酒、肿瘤转移无明显关系。而高/高-中分化胃癌患者与P53基因突变的相关性较高。本研究发现了一些新的P53基因突变，并在中国中南部地区人群中显示了P53和k-ras的突变模式和频率。
This case-control study investigated the mutations in p53 and k-ras genes of 123 gastric carcinoma patients and 129 normal individuals from Hunan, China. By isolating genomic DNA from peripheral blood and employing polymerase chain reaction-single strand conformation polymorphism and DNA sequencing, the mutations of p53 exons-5, 6, 7, and 8 and k-ras were detected. The overall mutation frequency of p53 was 29.3%, and mutation was found in all four exons studied. The point mutations were predominant and among them, G: C -> A: T was the highest (41.7%), followed by A: T -> G: C (25%), G: C -> C: G (11.1%), G: C -> T: A (8.3%), and A: T -> T: A (2.8%). The frameshift mutation was 11.1%. Mutations were detected in codons-131, 132, 133, 135, 149, 151, 162, 167, 173, 174, and 175 of exon 5, codons-193, 197, 213, and 215 of exon 6, codons-245, 246, 248, 249, and 270 of exon 7, and codons-271, 272, 273, and 282 of exon 8 of p53. The overall frequency of mutation in k-ras was 9.8%, mostly in codon-12 (91.7%) and in codon-13 (8.3%). There was no significant relationship between p53 and k-ras gene mutation in gastric carcinoma patients. Also, the relationships between p53 mutation and age, sex, smoking or drinking, and tumor metastasis were not significant. However, the patients with high/high-middle differentiated gastric carcinoma had a higher association with of p53 mutations. This study identified some novel p53 mutations in gastric cancer and showed mutation pattern and frequency of p53 and k-ras in the population of the central southern region of China.