散发性大肠癌K-ras基因点突变研究及其临床病理意义  

K-ras Oncogene Point Mutation in Sporadic Colorectal Carcinoma and its Clinicopathological Significance

作　　者：吴伟[1] 胡锦林[1] 鞠海星[2] 黄新[2] 孙文勇[1] 

机构地区：[1]浙江省肿瘤医院病理科[浙江省临床病理重点(扶持)学科],杭州310022 [2]浙江省肿瘤医院结直肠外科

出　　处：《医学研究杂志》2010年第12期53-57,共5页Journal of Medical Research

基　　金：浙江省自然科学基金资助项目(Y207427)

摘　　要：目的观察散性大肠癌K—ras基因12、13密码子点突变情况，探讨其与临床病理特征的关系。方法对2005～2009年问浙江省肿瘤医院确诊的140例大肠痛进行回顾性分析，并提取石蜡标本中癌组织DNA，经PCR扩增后应用焦磷酸测序技术检测K—ras基因第12、13密码子点突变情况。结果K—ras基因突变率397％（55／140），12密码子突变率78．2％（43／55），13密码子突变率21．8％（12／55）。共发现7种突变类型，包括12密码子（GGT→AT、GGT→AGT、GGT→TGT、GGT-→GTT、GGT→CGT、GGT→GCT）和13密码子（GGC→GAC），以12密码子（CGT→GAT）最常见，占突变总数41．8％（23／55）。K—ras基因突变与性别、年龄、大体类型、瘤体、原发部位、病理亚型、组织学分级、浸润深度、转移、Duke’S分期、脉管侵犯均无相关性（P〉0．05）；第12与13密码子突变在原发部位、淋巴结转移上差异有统计学意义（P〈0．05）。结论散发性大肠癌中K—ras基因突变率为39．7％，12密码子（GGT→GAT）突变是最常见类型。特定位点的突变与一些临床病理参数密切相关，其中12密码子突变在结肠癌中的发生率高，并易出现淋巴结转移。通过K—ras基因检测有助于指导临床开展大肠癌个体化治疗。Objective To investigate K - ras gene mutation at eodon 12 and codon 13 in sporadic colorectal carcinoma and reveal the correlation with the clinieopathological significance. Methods 140 cases of colorectal carcinoma from 2005 to 2009 were recruited from Department of Pathology, Zhejiang Cancer Hospital, China. Genomic DNA was extracted from paraffin -embedded colorectal carcino- ma tissues. K - ras gene point mutations were analyzed by pyrosequencing after polymerase chain reaction amplification. Results K - ras point mutation was detected in 55/140（39.7% ）. Of all 55 mutation cases, point mutation rate at codon 12 and eodon 13 was 78.2% and 21.8% respectively. In addition, seven types of K - ras mutation were found, including codon 12 （ GGT→GAT, GGT→AGT, GGT→TGT, GGT→GTT,GGT→CGT,GGT→GCT） mutation and codon 13 （GGC→GAC） mutation . The predominant mutation was GGT→GAT at co- don 12 mutation. K -ras gene mutations had no relationship with sex,age, tumor size,tumor location, histologic subtype,tumor grade, in- filtrating depth, metastasis,Duke＇s stage and vascular invation（ P 〉 0.05 ）. Statistical differences were observed for tumor location and lymph node metastasis with the type of K - ras mutation at codon 12 and codon 13 （P 〈 0.05 ）. Conclusion K - ras gene point mutation rate of sporadic eoloreetal carcinoma was 39.7%. The most commom types of K - ras mutation was codon 12（GGT--~GAT） mutation. Some spe- cial site of mutation was closely related with the clinicopathologic feature. Codon 12 mutation was frequently occured at colon carcinoma and asso- ciated with lymph node metastasis. K - ras gene detection was helpful for developing the clinical individual cancer treatment.

关 键 词：大肠癌 K—ras基因 点突变 临床病理 

分 类 号：R734.340.4[医药卫生—肿瘤]