乳腺良性疾病与线粒体DNA体细胞突变的相关性

Roles of mitochondrial DNA somatic mutations in the pathogenesis of benign breast disease： a perspective from whole genome study

目的基于线粒体DNA的全基因组信息研究线粒体DNA体细胞突变与乳腺良性疾病发生的相关性。方法对2010年9月至2011年6月来自云南昆明的28例良性乳腺疾病女性患者（年龄30—50岁，平均33岁）的病变组织及外周血，进行线粒体DNA全基因组序列的PCR扩增及DNA测序；以修订过的剑桥标准序列为标准并参照东亚线粒体DNA系统发育树记录突变位点，同时通过单倍型类群划分识别出私有突变与体细胞突变。结果28例患者中发现7个体细胞突变，其中1个位于控制区而另外6个均位于编码区，且存在于线粒体DNA编码区区段中的体细胞突变大部分（4／6）为非同义突变，其核苷酸的变异可引发编码氨基酸的变化。结论线粒体DNA突变在乳腺良性疾病的发生、发展中可能存在潜在的作用。

Objective To explore the potential roles of mitochondrial DNA somatic mutations in benign breast disease based on the entire genome of mitochondrial DNA and elucidate the relationship between benign breast disease and breast cancer. Methods The genomic DNA of tumor tissue and peripheral blood in 28 benign breast disease patients with an average age of 33 years （range： 30 -50） were extracted respectively. According to the revised Cambridge reference sequence and phylogenetic tree reconstruction, the mutations were identified and distinction was made between somatic mutations and private mitochondrial DNA mutations by haplogroup. Results Seven somatic mutations were detected. One mutation was located in the control region whereas the other six lied in the coding region. Further analyses revealed that, out of these 6 coding-region mutations, 4 were non-synonymous and would introduce the changes of amino acids. Conclusion The mutations of mitochondrial DNA may play potential roles in the occurrence and development of benign breast disease.