摘要
目的探讨转化生长因子β(TGF-β)Ⅱ型受体基因突变、微卫星不稳定性(MSI)在大肠腺瘤癌变过程中的作用。方法选用BAT-26微卫星位点应用PCR-SSCP银染方法鉴定大肠腺瘤及大肠癌组织MSI状态,并检测TGF-βⅡ型受体突变热点cDNA709-718在大肠腺瘤、大肠癌中的突变情况及其与大肠癌临床病理特征的关系。结果本实验选取的60例大肠癌中TGF-βⅡ型受体的突变率为26.7%(16/60),42例大肠腺瘤的突变率为11.9%(5/42),且均发生在伴中重度不典型增生的晚期腺瘤中。本组88.8%MSI大肠癌存在TGF-βⅡ型受体基因突变。TGF-βⅡ型受体突变与大肠癌临床病理特征间有密切关系,其多位于右半结肠,多发生在伴MSI的大肠癌,多为分化不良型腺癌,Duke’s A、B期患者比例显著高于Duke’s C、D期(P<0.05)。结论转化生长因子βⅡ型受体基因突变致细胞失去对TGF-β的生长抑制反应而发生肿瘤可能在大肠腺瘤癌变过程起着重要作用,其可能是MSI大肠癌发生的分子机制,且与大肠癌临床病理特征间有密切关系。
Objective To determine the relationship between the mutation of the TGF-β type Ⅱ receptor gene and microsatellite instability（MSI）in the tumorigenesis of colorectal cancer. Methods Selecting information-integrated fresh specimens of 60 colorectal carcinomas and 42 adenomas, the genomic DNA was extracted by phenol-chloroform procedure. Selecting BAT-26 as microsatellite marker to determine MSI of colorectal cancer, The mutation hot spot cDNA709-718 of TGF-β R Ⅱ was detected using silverstaining PCR-SSCP（single stranded conformation polyrnorphism）. Statistical analysis was performed by Chi-square and Fisher＇s exact test. Results The mutation of TGF-β R Ⅱ gene in the cDNA709-718 was found in 16/60（26. 7% ） of colorectal cancer, 5/42 （11.9% ） of colorectal adenomas, and only in adenomas with high-grade dysplasis. 88. 8% MSI colorectal cancers exist the mutation of TGF-βR Ⅱ gene. MSI colorectal cancers containing R Ⅱ mutation have features of poorly differentiated adenocarcinoma, tendency for right side involvement of the colon, rate of Dukes A and B stage higher than C and D. Conclusion Mutation of TGF-βRⅡ gene is the mechanism of the escape of colorectal cancer cells from negative growth control mediated by TGF-β, it plays an important role in the carcinogenesis of colorectal cancer.
出处
《肿瘤防治研究》
CAS
CSCD
北大核心
2006年第7期509-511,共3页
Cancer Research on Prevention and Treatment
关键词
转化生长因子Β
受体
突变
大肠腺瘤
大肠癌
Transforming growth factorβ
Receptor
Mutation
Colorectal neoplasm
Adenoma
