乳腺癌中线粒体基因组D环区基因突变的研究

Study on the relation between mutations in D-loop region of mitochondrial DNA and tumorgenesis of breast cancer

目的通过检测乳腺癌基因组D环区体细胞突变和种系性变异,探讨其与乳腺癌发生的关系。方法提取24例乳腺癌患者癌、癌旁组织及外周血细胞总DNA,PCR扩增各组织线粒体DNA(mitochondrial DNA,mtDNA)基因组D环(D-loop),基因测序后与线粒体文库中的剑桥序列比对,分析突变类型。结果在24例乳腺癌组织中,共发现91个种系性变异,11例(45.8%)肿瘤发现体细胞突变共19例次,36.8%位于第一高变区,52.6%位于第二高变区。结论乳腺癌mtDNA D环区具有高度多态性和高度突变率,该区的碱基改变在乳腺癌的形成中可能起重要作用。

Objective To investigate the potential role of mitochondrial DNA mutations in tumorigenesis of breast cancer and to analyze, somatic mutations and polymorphisms of mitochondrial D-loop region in breast cancer. Methods The D-loop of mitochondrial DNA in tumor samples, paired normal tissues and peripheral blood samples were amplified by PCR and sequenced. The sequences were compared with the Cambridge sequence reported in Mitomap to analyze the mutation types. Results Ninety-one germline variations were found in total 24 tumors. Eleven tumors （ 45.8% ） presented somatic mtDNA mutations with a total of nineteen. Among them, 36. 8% and 52. 6% were located in hypervariable segment 1 and 2 respectively. Conclusion Mitochondrial DNA D-loop has high polymorphisms and high somatic mutations. The variants of the region might play an important role in tumorgenesis of normal breast tissue.