胃癌、肠化生组织中TGF-β RⅡ、Bax基因突变与微卫星不稳定性

TGF-β RⅡ,Bax gene mutations and microsatellite instability in gastric cancer and intestinal metaplasia

目的:检测胃癌、肠化生组织中TGF-βRⅡ(RⅡ)和Bax基因突变与微卫星不稳定性(MSI)发生情况,了解其相关性,进一步探讨MSI在胃癌发生发展中可能的作用机制。方法:酚与氯仿法抽提胃镜下36例胃癌组织标本基因组DNA,二甲苯与蛋白酶K法提取51例肠化生组织石蜡标本基因组DNA,银染PCR-SSCP方法同时检测目的位点。结果:胃癌中RⅡ和Bax基因发生突变分别有7例和6例,MSI发生率达58.3%,两个基因突变均见于MSI阳性的胃癌,尤其是MSI-H型胃癌,而肠化生组织MSI发生率为17.6%,未见RⅡ和Bax基因发生突变。结论:MSI在肠化生-胃癌途径中发挥一定的作用,它可通过引起靶基因突变,特别是部分抑癌基因突变(如RⅡ和Bax基因),促进部分胃癌的发生发展。

Objective： By investigating mutations of TGF-β receptor type Ⅱ gene （ RⅡ）, Bax gene, and the changeable pattern of microsatellite instability（MSI） in gastric cancer（ GC ）and intestinal metaplasia（ IM ）, the potential mechanism of MSI in the development of GC was explored . nethods：Genomic DNA from thirty-six GC specimen was obtained by endoscopy and fifty-one IM sections cut from paraffin-embedded materials was respectively extracted by phenol-chlorform and xylene-proteinase K. PCR-SSCP（ single stand conformation polymorphism）was used to analyze gene mutations and MSI. Results：The mutations of RⅡ gene and Bax gene were found in 7and 6 cases of GC, respectively. MSI was identified in 58.3% （21/36） out of GC and 17.6% （9/15） out of IM. Among MSI positive tumors,7（ 19.2% ）showed MSI-H pattern. Two gene mutations were found in GCs with MSI ,especially in GCs with MSI-H. No mutation of RⅡ gene or Bax gene was found in IMS. Conclusions：MSI might be important in the development of GC, probably by inducing mutations of target genes such as RⅡ and Bax.