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中国湖南胃癌患者中p53和k-ras的基因突变

Genetic mutations of p53 and k-ras in gastric carcinoma patients from Hunan, China.

作者信息

Chen Han-Chun, Chen Hui-Juan, Khan Md Asaduzzaman, Rao Zhou-Zhou, Wan Xin-Xing, Tan Bo, Zhang Dian-Zheng

机构信息

Department of Biochemistry, School of Biological Science and Technology, Central South University, Changsha, Hunan 410013, China.

出版信息

Tumour Biol. 2011 Apr;32(2):367-73. doi: 10.1007/s13277-010-0129-2. Epub 2010 Nov 16.

Abstract

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.

摘要

本病例对照研究调查了123例来自中国湖南的胃癌患者和129名正常个体的p53和k-ras基因的突变情况。通过从外周血中分离基因组DNA,并采用聚合酶链反应-单链构象多态性和DNA测序技术,检测了p53基因第5、6、7和8外显子以及k-ras基因的突变。p53基因的总体突变频率为29.3%,在所研究的4个外显子中均发现了突变。点突变占主导地位,其中G:C→A:T突变比例最高(41.7%),其次是A:T→G:C(25%)、G:C→C:G(11.1%)、G:C→T:A(8.3%)和A:T→T:A(2.8%)。移码突变率为11.1%。在p53基因第5外显子的第131、132、133、135、149、151、162、167、173、174和175密码子,第6外显子的第193、197、213和215密码子,第7外显子的第245、246、248、249和270密码子,以及第8外显子的第271、272、273和282密码子中检测到了突变。k-ras基因的总体突变频率为9.8%,主要发生在第12密码子(91.7%)和第13密码子(8.3%)。胃癌患者中p53和k-ras基因突变之间无显著相关性。此外,p53基因突变与年龄、性别、吸烟或饮酒以及肿瘤转移之间的关系也不显著。然而,高中分化型胃癌患者与p53基因突变的相关性更高。本研究鉴定了胃癌中一些新的p53基因突变,并显示了中国中南部地区人群中p53和k-ras基因的突变模式及频率。

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