β-catenin基因在Peutz-Jeghers综合征组织中的突变及表达  

Mutation and expression of the β-catenin gene in Peutz-Jeghers syndrome

作　　者：占春玲 吴保平[2] 张亚历[2] 

机构地区：[1]长沙市第一医院感染二科,湖南省长沙市410005 [2]南方医科大学南方医院消化内科,广东省广州市510515

出　　处：《世界华人消化杂志》2011年第16期1739-1744,共6页World Chinese Journal of Digestology

摘　　要：目的:研究Peutz-Jeghers综合征(PJS)患者体内β-catenin基因突变及其蛋白表达,探讨β-catenin在PJS息肉发生及恶变中的作用.方法:收集PJS息肉、癌旁正常黏膜各12例,结肠腺瘤、结肠癌组织各14例,及相应PJS血液标本,检测β-catenin基因外显子3突变及mRNA表达水平.选取PJS息肉、结肠腺瘤、结肠癌、结肠正常黏膜组织石蜡标本各20例,通过免疫组织化学SP法检测β-catenin蛋白表达情况.结果:PJS息肉组织RT-PCRβ-cateninIA/GAPDHIA与结肠腺瘤、结肠癌、癌旁正常组织相比,差异无显著性.7例(70%)PJS息肉组织、2例(66.7%)PJS肠道正常黏膜、3例(50%)PJS血液白细胞出现编码区431位碱基缺失突变;8例(80%)PJS息肉组织、1(33.3%)例PJS肠道正常黏膜、4例(66.7%)PJS血液白细胞、2例(100%)PJS家族正常成员出现非编码区184位插入突变;1(50%)例PJS家族正常成员、2例(33.3%)PJS血液白细胞编码区421位缺失突变;2(20%)例PJS息肉组织非编码区189位插入突变.PJS、腺瘤、腺癌及正常组织中,β-catenin膜表达缺失率分别为30.0%、45.0%、75.0%和5.0%;细胞质阳性表达率和表达强度呈增加趋势;胞核阳性表达率分别为60.0%、30.0%、80.0%、5.0%;总的异位表达率分别为60.0%、50.0%、90.0%、5.0%,差异均具有显著性(P<0.05).结论:PJS患者β-catenin蛋白胞质内异常聚集并非mRNA表达量增高所致.PJS息肉组织中β-catenin基因突变较为常见,PJS不仅存在体系突变,也存在胚系突变,431、421、184、189这4个碱基位点可能是PJS有别于其他肿瘤的新的突变位点.β-catenin蛋白表达异常可能是PJS息肉形成及恶变的特征之一.AIM： To detect the gene mutation and protein expression of β-catenin in Peutz-Jeghers syndrome （PJS） to understand the role of β-catenin in the development, progression and canceration of PJS polyps. METHODS： （1） The β-catenin mRNA expression and mutations in exon 3 of the β-catenin gene were detected by RT-PCR and sequencing in 12 PJS polyp specimens, 14 colon adenoma specimens, 14 colon cancer specimens, and 12 normal colon tissue specimens. （2） The expression of β-catenin protein was examined immunohistochemically in 20 cases of PJS polyps, 20 cases of colon adenoma, 20 cases of colon carcinoma, and 20 cases of normal colon tissue. RESULTS： （1） The mRNA expression level ofβ-catenin relative to GAPDH in PJS showed no significant difference with those in colon adenoma, colon cancer, and normal colon tissue. （2） Gene deletion and insertion mutations were detected in PJS polyps. A deletion mutation at nucleotide 431, which might result in a frameshift or a premature stop codon, was detected in 70% of PJS patients. A T insertion mutation at nucleotide 184, which might result in abnormal regulation of protein synthesis, was detected in 80% of PJS patients. Similar mutations were also detected in the blood and normal colonic mucosa of PJS patients and health PJS family members. （3） Reduced membrane, cytoplasmic and nuclear expression of β-catenin was found in PJS polyps, colon adenoma, and carcinoma tissue. The overall rate of ectopic expression of β-catenin was 60.0% in PJS, which was significantly different from those in colon adenoma （50.0%）, carcinoma （90.0%） and normal mucosa （5.0%） （all P 0.05）. CONCLUSION： The abnormal cytoplasmic accumulation of β-catenin was not related with the elevation of β-catenin mRNA expression in PJS polyps. β-catenin gene mutations were common in PJS, especially the deletion mutation at nucleotide 431 and T insertion mutation at nucleotide 184. Abnormal β-catenin protein expression might be one of the characteristics of PJS

关 键 词：PEUTZ-JEGHERS综合征 Β-CATENIN 癌易感综合征 基因突变 蛋白表达 

分 类 号：R735.34[医药卫生—肿瘤]