Mutations in the D-loop region and increased copy number of mitochondrial DNA in human laryngeal squamous cell carcinoma
Mutations in the D-loop region and increased copy number of mitochondrial DNA in human laryngeal squamous cell carcinoma
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人喉鳞状细胞癌 D 环区域突变和线粒体 DNA 拷贝数增加
DOI：
10.1007/s11033-012-1939-7
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发表时间：
2013-01-01
影响因子：
2.8
通讯作者：
Huang, Zhigang
中科院分区：
文献类型：
--
作者：
Guo, Wei;Yang, Denghua;Huang, Zhigang
D-loop突变和mtDNA拷贝数改变在喉鳞状细胞癌中的作用尚不清楚。在此，我们研究了喉鳞状细胞癌中线粒体DNA的D-loop区体细胞突变和拷贝数改变的特点和作用。采用直接测序和实时荧光定量PCR技术检测40例喉鳞癌患者的喉鳞癌组织、癌旁正常组织和外周静脉血标本中D-loop突变和mtDNA拷贝数。采用t检验、方差分析和χ 2检验分析突变、mtDNA拷贝数改变与临床病理参数的关系。结果显示，21例（52.5%）肿瘤存在体细胞mtDNA D-loop突变，共34个突变。其中28例（82.4%）位于HVII，6例（17.6%）位于HVI. D-loop突变与肿瘤分化程度和p53突变相关（P< 0.05），mtDNA拷贝数增加。肿瘤组织和癌旁正常组织中mtDNA拷贝数均显著高于外周血（P< 0.05）。携带D-loop突变的病例mtDNA拷贝数显著高于阴性病例（P< 0.05）。这些结果表明，mtDNA D-loop在喉鳞状细胞癌中是一个不稳定的区域，体细胞突变和多态性频率高。与mtDNA拷贝数的增加一起，这些因素可能在喉癌的发生中起作用。
The effects of D-loop mutations and the mtDNA copy number alterations in LSCC are poorly understood. Herein, we investigated the features and roles of somatic mutations of the D-loop region and copy number alterations in mtDNA of LSCC. Using direct sequencing and real-time quantitative PCR, we examined D-loop mutations and mtDNA copy number in LSCC tissues, paracancerous normal tissues and peripheral vein blood samples from 40 LSCC patients. A student’sttest, ANOVA test and χ2test were used to analyze association among mutations, mtDNA copy number alterations with clinicopathologic parameters. The results revealed that 21 tumors (52.5 %) had somatic mtDNA D-loop mutations with a total of 34 mutations. Among them, 28 (82.4 %) and 6 (17.6 %) were located in HVII and HVI, respectively. D-loop mutations correlated with tumor differentiation and p53 mutation (P< 0.05), and increased mtDNA copy number. In addition, mtDNA copy number in tumor tissues and paracancerous normal tissues were all significantly higher than in peripheral blood (P< 0.05). The copy number of mtDNA in the cases which carried D-loop mutation was significantly higher than that of the negative cases (P< 0.05). These results suggest that the mtDNA D-loop in LSCC is an unstable region with a high frequency of somatic mutation and polymorphisms. Together with the increase in mtDNA copy number, these factors may play a role in carcinogenesis of the larynx.