Kamalidehghan Behnam, Houshmand Massoud, Ismail Patimah, Panahi Mehdi Shafa Shariat, Akbari Mohammad Hassan Hosseini
Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.
Arch Med Res. 2006 Aug;37(6):730-5. doi: 10.1016/j.arcmed.2006.02.005.
The aim of this study was to determine the frequency of delta mtDNA4977 in tumoral cells as compared with adjacent normal cells in gastric cancer.
In order to investigate whether a high incidence of mutation exists in mitochondrial DNA of gastric cancer tissues, we screened one of common region of the mitochondrial genome by PCR amplification and Southern blot followed by DNA sequence analysis. DNA isolated from these cells was used to amplify hypervariable regions ATPase8/6, COXIII, ND3, ND4 and ND5 of delta mtDNA4977.
In 107 cancer patients, delta mtDNA4977 was detected in 6 cases (5.60%) of the tumoral tissues and 18 cases (16.82%) of the non-tumoral tissues that were adjacent to the tumors. Levels of delta mtDNA4977 deletions were found to be more in non-tumoral tissues than in adjacent tumoral tissues. There was no correlation of patients with certain clinical parameters like age, sex, tumor location and tumor size; however, there was an obvious relationship with intestinal-type of gastric cancer.
Unknown genetic aspects, ambiguous environmental factors and reactive oxygen species (ROS) can cause the delta mtDNA4977 mutation rate to be increased in gastric cancer. The results suggest that percentage level of delta mtDNA4977 is less common and intolerable in tumoral tissue, probably because of high metabolism and ROS generation. We supposed that the cells initially had delta mtDNA4977 transform to tumoral cells and the existed deletion conferred metabolic disadvantage; thus, cells containing such a mtDNA deletion would be overgrown by other cancer cells without this mtDNA deletion. As a result, the presence of delta mtDNA4977 will be low in tumoral cells.
本研究的目的是确定胃癌肿瘤细胞中与相邻正常细胞相比,线粒体DNA 4977缺失(delta mtDNA4977)的频率。
为了研究胃癌组织线粒体DNA中是否存在高突变率,我们通过聚合酶链反应(PCR)扩增和Southern印迹法筛选线粒体基因组的一个常见区域,随后进行DNA序列分析。从这些细胞中分离的DNA用于扩增delta mtDNA4977的高变区ATPase8/6、COXIII、ND3、ND4和ND5。
在107例癌症患者中,肿瘤组织中有6例(5.60%)检测到delta mtDNA4977,与肿瘤相邻的非肿瘤组织中有18例(16.82%)检测到。发现非肿瘤组织中delta mtDNA4977缺失水平高于相邻肿瘤组织。患者与年龄、性别、肿瘤位置和肿瘤大小等某些临床参数无相关性;然而,与肠型胃癌存在明显关系。
未知的遗传因素、不明确的环境因素和活性氧(ROS)可导致胃癌中delta mtDNA4977突变率增加。结果表明,delta mtDNA4977的百分比水平在肿瘤组织中不太常见且难以耐受,可能是因为高代谢和ROS生成。我们推测最初具有delta mtDNA4977的细胞转变为肿瘤细胞,而存在的缺失赋予代谢劣势;因此,含有这种线粒体DNA缺失的细胞将被其他没有这种线粒体DNA缺失的癌细胞过度生长。结果,肿瘤细胞中delta mtDNA4977的存在将很低。