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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。
Objective: To investigate the differences of mitochondrial DNA somatic mutations in patients of different races. Methods: Tumor samples from 2000/2003 were collected from 54 Chinese Han nationality patients and 19 Caucasian American patients with breast cancer and normal breast tissues more than 5 cm from the edge of the tumor by using phase-temperature gradient gel electrophoresis Organization for prospective mutation analysis. 32 pairs of overlapping primers were used to amplify mitochondrial full length genes from all patient’s tumor tissues and paired normal tissues. DNA fragments of different electrophoresis band types in tumors and normal tissues were sequenced to identify the types of mutations. RESULTS: Somatic cell mitochondrial DNA mutations were found in 747% (14/19) Caucasian breast cancers, with somatic mutations of only 37% (24/54) of breast cancers among Han Chinese, but the latter were not documented in the MitoMap database The number of new mutations was significantly more than the former. Mutation density was the highest in D-ring in both groups. The mutation density of rRNA in Han was higher than Caucasians, but lower in D-ring (χ2 = 9.27, P = 0.026). Conclusion: The frequency of somatic mutations in mitochondrial genomes, the distribution of mutations and the density of mutations in each gene region are different in Chinese Han and American Caucasian breast cancer patients. In Chinese Han population, there are more new mutations in breast cancer patients not recorded in the MitoMap database, which shows that Han people have different characteristics of somatic mutation of mitochondrial genes from Caucasians. This study provides a theoretical basis for preventive cancer intervention.