转化生长因子βⅡ型受体基因突变在大肠腺瘤癌变过程中的作用
Mutation Analysis of Transforming Growth Factor β Ⅱ Receptor Gene in Colorectal Adenoma Carcinogenesis
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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。Abstract: 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 silver-staining PCR-SSCP(single ...
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