胃癌组织线粒体DNA D-loop区的突变及其意义

D-loop MITOCHONDRIAL DNA MUTATION IN GASTRIC CANCER AND ITS SIGNIFICANCE

目的研究胃癌组织中线粒体DNA(mtDNA)D-loop区突变情况及其在肿瘤发生和发展中的作用。方法选择17例胃癌及相应正常胃黏膜组织,应用聚合酶链反应(PCR)对其mtDNA D-loop区进行扩增并测序,将测序结果与线粒体文库中的Revised Cambridge Reference Sequence(rCRS)进行对比分析。结果 17例胃癌组织中共发现mtDNA D-loop区存在175个多态性变异,其中8个(4.6%)为新发现的变异。8例(47.1%)胃癌组织中共发现13次突变;突变热点集中在HV1(23.1%)和HV2(53.9%),并且HV2较HV1更易突变。mtDNA D-loop区突变率与胃癌分化程度、浸润深度、有无淋巴结转移、病人性别和年龄无关(P>0.05)。结论 mtDNA D-loop区尤其是其中的HV1及HV2是一个具有高度多态性和突变性的区域,在胃癌中突变率较高。

Objective To study the mitochondrial DNA（mtDNA） mutation in D-loop region in gastric cancer and its effect on tumorigenesis and development. Methods Polymerase chain reaction（PCR） and sequencing were applied to detect the D-loop region of mitochondrial genome in 17 gastric cancer specimens and corresponding non-cancerous tissue of the stomach.The sequence was compared with the Revised Cambridge Reference Sequence in Mitomap. Results In the tissue of 17 cancer cases,175 polymorphisms were found in D-loop region of mtDNA,in which,eight（4.6%） were a new mutation.Thirteen mutations were observed in eight（47.1%） of the 17 cases.HV1（23.1%） and HV2（53.9%） were mutational hot spots,with HV2 being more susceptible to mutation.The mutation in D-loop region of mtDNA was not associated with cell differentiation,depth of infiltration,whether or not with lymph not metastasis of the cancer,and not related with the gender and age of the patients. Conclusion The D-loop region of mtDNA,especially of HV1 and HV2,is highly polymorphic and mutable,and the mutation rate is relatively high in gastric cancer.