结直肠癌患者肿瘤组织中KRAS、BRAF基因突变观察及分析  

Observation and analysis of KRAS,BRAF gene mutation in tumor tissues of colorectal cancer

作　　者：孙毅[1] 艾尼瓦尔.艾木都拉 古丽比也.沙比尔 肖蕾[1] 杨颖[1] 包永星[1] 

机构地区：[1]新疆医科大学第一附属医院,乌鲁木齐830000

出　　处：《山东医药》2014年第43期8-11,共4页Shandong Medical Journal

基　　金：吴阶平医学基金资助项目(320.6799.1143);新疆医科大学第一附属医院科研奖励基金资助项目(2011YFY11);新疆乌鲁木齐市科学技术计划项目(H111313001)

摘　　要：目的观察结直肠癌患者肿瘤组织中KRAS和BRAF基因的突变情况,并分析其与患者临床病理特征的关系。方法经病理检查确诊的结直肠癌患者100例,留取手术切除的肿瘤组织标本,采用直接测序法检测其中的KRAS基因外显子2第12、13位密码子以及BRAF基因外显子15的突变状态,分析基因突变与患者临床病理特征的关系。结果本组患者KRAS、BRAF基因突变率分别为28%(28/100)、5%(5/100),BRAF基因在KRAS野生型患者中的突变率为5.6%(4/72)。KRAS基因突变类型共有8种,以G12D、G12V及G13D最常见;BRAF基因突变类型共有3种,以V600E最常见。KRAS基因在≥60岁患者中的突变率高于<60岁患者(P<0.05),且在肿瘤原发灶分化程度较高的患者中突变率高(P<0.05);而BRAF基因在肝转移灶直径越大的患者中突变率升高越明显(P<0.05)。KRAS及BRAF基因突变与原发灶部位均有关(P均<0.05)。结论结直肠癌患者肿瘤组织中KRAS基因突变率较高,KRAS基因突变与患者年龄、原发灶组织学分级、肝外侵犯或转移及原发灶部位相关,而BRAF基因突变与肝转移灶最大直径和原发灶部位有关。Objective To observe KRAS , BRAF gene mutational status in tumor tissues of colorectal cancer patients and to analyze the correlation between mutation and clinicopathological feature .Methods Collected surgical removed tumor tissue samples from 100 cases of colorectal cancer patients , which were diagnosed by histological examination .Codons 12, 13 on exons 2 of KRAS genes and exons 15 of BRAF genes were detected by PCR-direct sequencing , to certificate the association between gene mutation and clinicopathological feature of patients .Results KRAS and BRAF mutations were present in 28%（28/100） and 5%（5/100） of patients, respectively.5.6%（4/72） samples were observed in mutation in wild-type BRAF patients.There were 8 types of mutation on KRAS genes , which were most common as G12D, G12V and G13D.Whereas, the BRAF gene mutation had 3 types and V600E was considered as the most prominent one .Mutation rate of KRAS genes was certificated higher in group of olds aged over 60 years than the rest（P〈0.05）.In addition, a significant increase mutation rate occurred in patients with primary tumors in high differentiation and extrahepatic invasion or metastasis （ P〈0.05） .How-ever, BRAF genes mutation rate obviously increased in patients with bigger diameter of liver metastatic lesions （P〈0.05）. KRAS and BRAF gene mutations were in association with primary tumor sites （all P〈0.05）.Conclusion There is a higher mutation rate on KRAS genes in tumor tissues of colorectal cancer patients , which is considered as in relation to factors of age, histological grade of primary tumor , extrahepatic invasion or metastasis and primary site .Mutation of BRAF genes is as-sociated with the maximum diameter of liver metastasis and primary tumor sites .

关 键 词：KRAS基因 BRAF基因 基因突变 表皮生长因子受体 结肠肿瘤 直肠肿瘤 

分 类 号：R739.5[医药卫生—肿瘤]