中国汉族人与美国高加索人乳腺癌患者线粒体基因细胞突变的比较  

Comparison of mitochondrial DNA somatic mutation in patients with breast cancer between Chinese Han people and American Caucasians

作　　者：谭端军[1] 刘玲玲[1] 徐斌[1] 赵玉生[1] Lee-Jun C Wong 

机构地区：[1]解放军总医院老年心血管病研究所,北京市100853 [2]美国华盛顿乔治城大学医学中心分子与人类遗传研究所,20007

出　　处：《中国临床康复》2005年第14期114-116,共3页Chinese Journal of Clinical Rehabilitation

基　　金：解放军总医院院长基金资助(03YZJJ005)~~

摘　　要：目的:探讨不同种族乳腺癌患者线粒体DNA体细胞性突变的差异。方法:利用时相温度梯度凝胶电泳方法对2000/2003所保存的肿瘤样本中,随机抽取的54例中国汉族人和19例美国高加索人乳腺癌患者乳腺组织和距肿瘤边缘5cm以上的正常乳腺组织进行前瞻性突变分析研究。采用32对重叠引物扩增了来自所有患者的肿瘤组织和配对正常组织的线粒体全长基因,对肿瘤和正常组织中不同的电泳条带类型的DNA片段进行测序以辩明其突变类型。结果:747%(14/19)高加索人乳腺癌具有体细胞性线粒体基因突变,汉族人中乳腺癌体细胞性突变的发生率仅37%(24/54),但后者未记录于MitoMap数据库的新突变数明显多于前者。两组均以D环区突变密度最高,汉族人rRNA区突变密度高于高加索人,而D环区则较之为低(χ2=9.27,P=0.026)。结论:中国汉族人与美国高加索人乳腺癌患者线粒体基因体细胞性突变频率、各基因区域的突变分布和突变密度具有一定的差异。在中国汉族人群乳腺癌患者出现较多的未记录于MitoMap数据库的新突变,显示出汉族人具有与高加索人不同的线粒体基因体细胞性突变特征。本研究为肿瘤预防性干预提供理论依据。AIM: To investigate the diversity of mitochondrial DNA (mtDNA) somatic mutatio n in patients with breast cancer of different races. METHODS: The mtDNA of breast cancer and corresponding normal tissues were extr acted from 54 Chinese Han people and 19 American Caucasians, whose tumor samples were reserved during 2000 to 2003, for prospective mutation analysis with tempo ral temperature gradient gel electrophoresis (TTGE). The entire mtDNA of all the subjects were amplified by using 32 pairs of overlapping primers. The mtDNA fra gments showing different banding patterns between tumor and normal tissue were s equenced to identify the exact mutations. RESULTS: 74%(14/19) of the tumors in American Caucasian showed somatic mtDNA mutation, while it was only 37%(24/54) in the Chinese Han people, and the latte r had more number of new mutation which was not recorded in the MitoMap database . The somatic mutation densities were the highest in the D loop region of both groups, and the mutation density in the rRNA region was higher but in the D loo p region was lower in the Chinese Han people than in the American Caucasians (χ 2=9.27, P=0.026). CONCLUSION: There are differences of mtDNA somatic mutation in frequency, dens ity and distribution between Chinese Han people and American Caucasians.The Chin ese Han patients with breast cancer have more new mutations which was not record ed in the MitoMap database, indicating that Han people have different characteri stics of mtDNA somatic mutation as compared with the American Caucasians. This s tudy has provided theoretical evidence for the preventive intervention of tumor.

关 键 词：线粒体/遗传学 DNA 线粒体 乳腺肿瘤/遗传学 突变 基因 高加索人种 

分 类 号：R73[医药卫生—肿瘤]