人肺癌组织线粒体ATPase 6基因突变研究

目的：了解人肺癌组织ATPase6基因变异,探讨线粒体DNA（mitochondrial DNA,mtDNA）突变与肿瘤发生的关系。方法：采用酚-氯仿法提取肺癌组织总DNA,用PCR产物直接测序方法,对37例肺癌组织mtDNA ATPase6基因序列进行分析,运用DNAStar软件将所得序列与mtDNA剑桥修订序列进行对照。结果：共发现28个碱基序列变异,没有检测到新的多态性位点,各亚型间在ATPase6基因碱基变异率没有显著性差异。在24例肺癌病例的ATPase6基因中检测到了碱基突变,突变率为64.8%。结论：在肺癌组织中存在ATPase6基因的高频率变异,这种变异可能在肺癌发生、发展中发挥重要作用。对ATPase6基因突变的进一步研究将有助于评价肺癌的DNA损伤和恶性程度,进一步研究这些变异对细胞功能的影响可能有助于阐明线粒体在肿瘤发生中的作用。

Mutations of ATPase6 gene from human lung cancer tissues

Objective：To know the variations of ATPase6 gene in human lung cancer tissues and to inquire into the relationship between mutations of mitochondrial DNA and carcinogenesis.Methods： Total DNA was extracted from lung cancer tissues from 37 patients using phenol/chloroform and was studied with DNA direct sequencing for DNA sequence variation within the ATPase6 gene.The DNA sequences were compared with human mitochondrial DNA revised Cambridge reference sequence.Results： Twenty eight variant sites were indentidified,and no new polymorphisms were detected in lung cancer,nor was there any association between variants and the three histopathological subtypes.Mutations of the ATPase6 gene were found in 24/37（64.8%） of the tested lung cancer samples.Conclusion： There is a high incidence of ATPase6 gene mutations in human lung cancer,indicating that ATPase6 gene mutations may play an important role in development and progression of lung cancer,which may be helpful in evaluating the damage to mtDNA and the degree of malignancy in lung cancer.Thus the study of the functional impact of these variants on cell behavior may elucidate the role of mitochondria in carcinogenesis.