鼻咽癌患者组织及血液中线粒体DNA D-loop区突变

目的:检测鼻咽癌患者线粒体DNA复制控制区(mtDNAD-loop)的突变情况。方法:以健康人血标本和鼻咽癌患者癌旁组织作为对照,对20例鼻咽癌组织样本及相应的血液样本的mtDNAD-loop区进行PCR扩增和直接测序分析。结果:在20份鼻咽癌组织样本中共发现312个核苷酸改变,其中293个为已知的多态性改变,4个为新的未记载过的多态性改变;9个肿瘤组织样本和相应的血标本中共发现15个突变;癌旁组织较多多态性变化,未检出突变;鼻咽癌的mtDNAD-loop区突变率为45%(9/20)。结论:血液中mtDNAD-loop的变异可能与鼻咽癌的易感性有一定的联系;本研究为寻找新的肿瘤基因诊断和肿瘤遗传易感性的标志物提供了依据。

High frequent mutations in the D - loop region of mitochondrial DNA in the nasopharyngeal carcinoma

Objective:To investigate the frequency of mitochondrial DNA (mtDNA)D-loop mutations in nasopharyngeal carcinoma (NPC). Methods: The D-loop region of mtDNA in 20 nasopharyngeal carcinoma tissues, matched with normal tissues and blood samples from the same patients was amplified with desighned primer by PCR . The mutations of products were examined by direct sequencing. Results: Somatic mtDNA mutations were detected in 45% (9 of 20) tumor samples and their matched blood samples were found with single or multiple changes, 4 out of 312 homoplasmic variations in our research group were previously unknown polymorphisms. A change A73G in all patients samples by sequencing comparison to the mitomap database; it might a special point mutation in Chinese NPC. No mutation was found in 10 health persons' blood samples. Conclusion: mtDNA D-loop region is a highly polymorphoric and mutable region in nasopharyngeal carcinoma. It is suggests that the D-loop region of mtDNA might play a significant role in nasopharyngeal carcinoma tumorigenesis.