肾癌患者线粒体基因组D环区基因突变的研究

目的：通过检测肾癌基因组 D 环区体细胞突变及种系性变异情况,探讨其与肾癌发生的关系。方法选取肾癌患者20例,对其癌组织、癌旁组织及外周血细胞总 DNA进行 PCR扩增并测序,相关结果与线粒体文库中剑桥序列进行比对,综合分析基因突变类型。结果在20例肾癌患者各组织中,共有7例检出线粒体DNA（mitochondrial DNA,mtDNA）的D-环区（displancement loop,D-Loop）存在突变,突变发生率为35%,涉及突变位点17个,其中4个属微卫星不稳定序列；20例患者中共发现9个基因库未记载的新的多态性变化。结论肾癌患者mtDNA的D环区具有高度多态性和高度突变率,该区的基因突变在肾癌的形成中可能发挥重要作用。

Study on the relation between mutations in D-loop region of mitochondrial DNA and tumorgenesis of renal cell carcinoma

Objective To investigate the potential role of mitochondrial DNA mutations in tumorigenesis of re-nal cell carcinoma and analyze somaticmutations and polymorphisms of mitochondrial D-loop region in renal cell carcinoma.Methods The D-loop of mitochondrial DNA in tumor samples,paired normal tissues and peripheral blood samples were amplified by PCR and sequencing.The sequences were compared with the Cambridge sequence reported in Mitomap to analyze the mutation types.Results Seven variations were found in total 20 tumors.Muta-tion rate was 3 5%,1 7 point mutations,of which 4 are microsatellite instability.Nine of the new gene pool was not recorded in the polymorphism changes in total 20 tumors.Conclusion Mitochondrial DNA D-loop has high poly-morphisms and high somatic mutations.The variants of the region might play an important role in tumorgenesis of renal cell carcinoma.