原发性非小细胞肺癌中K-ras基因突变的研究  

Detection of K－ras Codon 12 Mutation in Patients with Non－Small Cell Lung Cancer

作　　者：关赛芳[1] 廖美琳[1,2] 丁嘉安[1,3] 许凯黎[1] 陈复华[1] 周瑾[1] 范锡凤 

机构地区：[1]上海市肿瘤研究所生化免疫诊断室,上海市200032 [2]上海市胸科医院 [3]上海市肺科医院

出　　处：《中国肿瘤临床》2001年第1期5-8,共4页Chinese Journal of Clinical Oncology

基　　金：上海市科委及上海市医学领先学科基金!(984119002)

摘　　要：目的：探讨非小细胞肺癌（Non－small cell lung cancer NSCLC）组织中K－ras第12密码子点突变与NSCLC发生和发展的相关性。方法：采用针对K－ras基因第12密码子特异点突变方式的引物进行PCR及银染法，分析175例新鲜NSCLC手术切除标本、43例癌旁组织及5例良性肺部疾患组织中K－ras基因第12密码子中CGT、GTT和GAT三种不同点突变方式。结果：175例NSCLC组织中出现K－ras 12密码子GGT→CGT突变率为34．86％（61／175），GGT→GTT突变率40．57％（71／175）及GGT→GAT突变率37．71％（66／175），总突变率为62．3％（109／175）。其中，同时出现CGT／GTT二个点突变为10．1％ 11／109CGT／GAT 9．2％10／109 GTT／GAT 12．8％ 14／109，而 CGT／GTT／GAT均出现突变占23．9％26／109。其中Ⅰ期、 Ⅱ期、Ⅲ期突变率分别为64．3％、56．8％及64．0％，另外腺癌突变率为63．8％、鳞癌为60．5％及腺鳞癌为64．5％因此K－ras点突变与肺癌的分期及病理类型均无相关性（P＞0．05）。然而，37例腺癌突变组中出现GTT／GAT突变率为17．2％ 10／58明显高于鳞癌的3．5％3／86二者具有明显差异（P＜0．01）。43例癌旁组织与5例良性肺部疾患组织均未发现K－ras点突变。Objective To study the relationship between codon 12 K－ras mutation and the pathogenesis of non－small cell lung cancerNSCLC． Methods Using a sensitive allele－specific codon 12 K－ras polymerase chain reaction assay and silver stain to analyze three kinds of mutation at codon 12 of K－ras gene CGT GTT and GAT in 175 NSCLC samples． Results 109 of 175 cases 62．3％ with NSCLC had codon 12 K－ras mutation． Among them CGT mutation was observed in 61 of 175 cases 34．86％ GTT mutation in 71 cases 40．57％ and GAT mutation in 66 cases 37．71％． Both the CGT／GTT mutations happened in 11 cases CGT／GAT in 10 cases and GTT／GAT in 14 cases respectively． 26 of 109 cases were found in all three kinds of mutation at codon 12 K－ras． There was no codon 12 K－ras mutation to be found in 43 surrounding non－cancerous lung tissues and 5 benign lung tumors． Since codon 12 K－ras mutation in patients with stage Ⅰ Ⅱ and Ⅲ were 64．3％36／56 56．8％25／44 and 64．0％48／75 respectively and K－ras mutation occurred in 63．8％ patients with adenocarcinoma 60．5％ patients with squamous cell carcinoma and 64．5％ patients with adenosquamous cell carcinoma． There was no significant difference found between the frequency of K－ras mutation and the pathological types or TNM staging of NSCLC P＞0．05． However the rate of both GTT and GAT mutations were higher in adenocarcinoma 27．03％ 10／37 than those in squamous cell carcinoma 5．77％ 3／52P＜0．01． Conclusion Codon 12 K－ras mutation occurres commonly in human NSCLC． Two or three different K－ras mutations can be found in some patients while GTT／GAT mutations are more frequently found in adenocarcinoma than those in squamous cell carcinoma P＜0．01． It is suggested that K－ras mutation may play a very important role in pathogenesis of human lung cancer．

关 键 词：非小细胞肺癌 NSCLC K-ms基因 点突变 PCR 

分 类 号：R734.2[医药卫生—肿瘤] Q754[医药卫生—临床医学]