大肠腺瘤、腺癌中DCC基因表达与201密码子点突变的研究  

DCC Gene Protein Expression and Codon 201 Mutation in Colorectal Adenoma and Carcinoma

作　　者：吴文溪[1] 伍世余[1] 

机构地区：[1]南京医科大学第一附属医院普外科,210029

出　　处：《实用癌症杂志》2004年第3期254-258,共5页The Practical Journal of Cancer

摘　　要：目的　探讨国人大肠腺瘤、腺癌中结直肠缺陷 (DCC )基因蛋白表达与该基因 2 0 1密码子的突变情况 ,及其与大肠肿瘤临床病理因素的关系。方法　采用免疫组织化学和PCR结合限制性酶切多态性分析 (PCR RFLP)方法 ,检测 3 0例正常大肠黏膜、40例大肠腺瘤、46例大肠癌及相应癌旁黏膜组织中DCC基因蛋白表达及 2 0 1密码子突变情况。结果　DCC蛋白在正常大肠黏膜、腺瘤组织及癌组织中阳性表达率分别为 10 0 %、83 %和 2 8% ,三者比较 ,均有显著性差异 (P <0 .0 5 )。腺瘤伴重度不典型增生者DCC蛋白表达缺失率 ( 5 5 % )明显高于腺瘤伴轻、中度不典型增生者 ( 3 % )。DukesC、D期大肠癌DCC基因蛋白表达缺失率明显高于DukesA、B期。腺瘤伴重度不典型者 2 0 1密码子突变率 ( 64 % )明显高于腺瘤伴轻、中度不典型增生者 ( 2 1% ) (P <0 .0 5 ) ;大肠癌突变率最高达 78% ;DukesC、D期大肠癌 2 0 1密码子突变率明显高于A、B期 ;大肠癌DCC基因 2 0 1密码子纯合突变率( 5 0 % )显著高于癌旁黏膜 ( 6% ) ,有显著性差异。 2 0 1密码子突变与患者性别、年龄、肿瘤组织学分型等因素无关。结论　大肠腺瘤向癌演变的过程中DCC基因 2 0 1密码子突变率和蛋白表达缺失率逐渐增高 。Objective To explore the DCC(dreleted in colorectal cacinoma) gene protein expression and the point mutation of codon 201 in colorectal adenoma and carcinoma,and to identify its correlation with clinicopathological characteristics of colorectal tumor.Methods The DCC protein expression was examined with immunohistochemical technique,and the point mutation of codon 201 was detected by polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP) in samples of 30 case of normal colon mucosa,40 cases of colorectal adenoma,46 cases of colorectal cancer and the corresponding tumor-adjacent mucosa.Results DCC protein expression rate was 100%,83% and 28% in normal colon mucus,colorectal adenoma and carcinoma,respectively(P<0.05).Colorectal adnoma with severe desplasia had a markedly lower DCC protein expression than adenoma with mild or moderate desplasia(P<0.05).In colorectal carcinoma,DCC protein expression rate was higher in Dukes A and B stages diseases than in Dukes C and D stages diseases(P<0.05).The frequency of codon 201 mutation was significantly higher in the adenoma with severe dysplasia than in the adenoma with mild and mediate desplasia(64% v.s.21%).Mutation rate of codon 201 in carcinoma was 78%.The point mutation rate was significantly higher in Dukes C and D stage carcinoma than in Dukes A and B stage carcinoma.The homozygous mutation rate of codon 201 was significantly higher in tumor tissues(50%) than in the matched tumor-adjacent mucosa(6%).The mutation rate of codon 201 had no relationship with gender,age,the histological type and the differentiation degree of the tumor.Conclusion The frequency of point mutation of codon 201 and the loss expression of DCC protein increased in adenoma-carcinoma sequence.It also indicates a tendency of the development and metastasis in colorectal carcinoma.

关 键 词：大肠腺瘤 腺癌 DCC基因 基因表达 201密码子 点突变 免疫组织化学 

分 类 号：R735.34[医药卫生—肿瘤] R736[医药卫生—临床医学]