摘要
目的:探讨线粒体DNA体细胞性突变和种系性变异在食管癌的发生情况及其可能的作用. 方法:利用时相温度梯度电泳方法分析了食管癌的线粒体基因体细胞性突变.采用32对重叠引物扩增了来自20例食管癌患者的肿瘤组织和配对正常组织的线粒体全长基因,在肿瘤和正常组织中不同的电泳条带类型的DNA片段被测序以辩明其突变类型. 结果:在20例肿瘤中11例(55%)至少发现一个体细胞性突变,总共发现14个体细胞性突变,其中1个位于rRNA (7.1%),4个位于mRNA(28.5%),另外9个位于高变D环区(64.3%).4个新的体细胞性突变中2个为错义突变.在测序片段中共发现187个种系性变异,其中14个为新发现的变异,173个为已被报道并记录在线粒体基因数据库中. 结论:食管癌患者线粒体DNA存在高发生频率的体细胞性突变提示线粒体DNA的变异可能与食管癌的发生发展有关.
AIM: To detect somatic mutations in the complete mito-chondrial genome and to investigate the role of mtDNA in the tumorigenesis of esophageal cancer. METHODS: A temporal temperature gradient gel electro-phoresis (TTGE) method was used to analyze the somatic mitochondrial DNA (mtDNA) mutations in esophageal cancer. The entire mitochondrial genomes in 20 tumor samples and paired normal tissues were amplified by using 32 pairs of overlapping primers. DNA fragments showing different banding patterns between normal and tumor mtDNA were sequenced to identify the somatic mutations and germline variations. RESULTS: Eleven out of the 20 tumors (55%) displayed at least one somatic mtDNA mutation. Total fourteen somatic mutations were found. Among them, one was in tRNA (7.1%), 4 in mRNA (28.5%), and 9 in the hypervariable D loop region (64.3%). There were two missense mutations in four novel somatic mutations. A total of 187 distinct germline variations were identified. Fourteen of these variations were novel, and 173 of them had been recorded in the Mitomap database. CONCLUSION: The high incidence of mtDNA mutations presents in patients with esophageal cancer. mtDNA alterations may play an important role in tumorigenesis of esophageal cancer.
出处
《世界华人消化杂志》
CAS
2004年第4期892-896,共5页
World Chinese Journal of Digestology
基金
解放军总医院院长基金资助项目
No.03YZJJ005~~
