线粒体DNA损伤与胃癌发生关系的研究

Relationship between injury of mitochondrial DNA and gastric carcinogenesis

目的:检测胃癌线粒体DNA(mitochondrial DNA,mtDNA)的突变和不稳定性,探讨mtDNA损伤与胃癌发生的关系及其作用机制。方法:采用PCR扩增22例胃癌组织和对应的远端正常胃黏膜组织mtDNA控制区(D-loop)以及编码基因,利用变性高效液相色谱(denaturinghigh performance liquid chromatography,dHPLC)和DNA测序检测分析mtDNA的变异情况(包括种系性突变、体细胞突变和不稳定性)。结果:22例胃癌组织其线粒体不稳定性(mitochondrial genome instability,mtGI)的发生(13/22,59.1%)与mtDNA体细胞突变(10/22,45.5%)呈正相关,r=0.894 4,χ2(Pearson未校正法)=14.400 0,P=0.000 1。肠型胃癌患者12S rRNA位点损伤度(每例2.32个/1 000 bp)是弥漫型胃癌(每例0.86个/1 000 bp)的2.7倍,t=2.638 6,P=0.015 8。结论:mtDNA损伤可能参与肠型胃癌的发生,mtDNA损伤致癌可能需要2次打击激活。

OBJECTIVE： To study the correlation of mtDNA＇s damage and gastric carcinogenesis by detecting mitochondrial genomic mutations and instabilities （mtGI） in gastric carcinomas. METHODS： Mitochondrial control region and some encoding genes of 22 samples in gastric cancer tissues and 22 coresponding normal gastric mucosa taken from the distal portion of surgical specimens were PCR am plified, Denaturing high performance liquid chromatography （dHPLC） was performed to analyze variations of those genes followed by sequencing. RESULTS： The mtGI frequence of 22 gastric cancers （13/22,59. 1%） was positively correlated with mitochondrial somatic mutation （ 10/22,45.5 %）, r = 0. 894 4, P=0. 000 1. And the injuried frequence of 12S rRNA Locus in intestinal type of gastric cancer was 2.7 fold than that in diffusive type （t=2.638 6,P=0.015 8）. CONCLUSION： The mtDNA injury may be involed in gastric carcinogenesis, presuming thai the twice hit mutation may be needed to activate the mtDNA＇s carcinogenesis.