Novel heteroplasmic frameshift and missense somatic mitochondrial DNA mutations in oral cancer of betel quid chewers
Novel heteroplasmic frameshift and missense somatic mitochondrial DNA mutations in oral cancer of betel quid chewers
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DOI：
10.1002/gcc.10217
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发表时间：
2003-06-01
影响因子：
3.7
通讯作者：
Wong, LJC
中科院分区：
文献类型：
--
作者：
Tan, DJ;Chang, J;Wong, LJC
线粒体 DNA (mtDNA) 由于对 DNA 氧化损伤高度敏感且修复机制有限，因此被认为与癌症发生有关。为了研究体细胞mtDNA突变在口腔癌肿瘤发生中的潜在作用，我们通过时间温度梯度凝胶电泳法筛选mtDNA突变的发生。我们使用 32 对重叠引物扩增了整个线粒体基因组，为了识别突变，我们对显示正常线粒体 DNA 和肿瘤线粒体 DNA 之间不同带型的 DNA 片段进行了测序。 18 例口腔癌中有 14 例 (77.8%) 显示体细胞 mtDNA 突变，总共 26 个突变。其中，6个位于mRNA编码区。三个是 NADH 脱氢酶亚基 2 中的错义突变（C14F、H186R、T173P），一个是细胞色素 c 氧化酶亚基 III 中的移码突变 9485delC。八个（44%）肿瘤在 D 环的核苷酸位置 303-309 聚 C 区中存在插入或缺失突变。还观察到多个大缺失。我们的结果表明体细胞 mtDNA 突变发生在口腔癌中。一些错义和移码突变可能在这种癌症的肿瘤发生中发挥重要作用。为了确定这些体细胞突变的病理效应，需要更广泛的生化和分子研究。 (C) 2003 Wiley-Liss, Inc.
Mitochondrial DNA (mtDNA) has been proposed to be involved in carcinogenesis because of its high susceptibility to oxidative DNA damage and limited repair mechanisms. For investigation of the potential role of somatic mtDNA mutations in the tumorigenesis of oral cancer, we screened the occurrence of mtDNA mutations by the temporal temperature gradient gel electrophoresis method. We amplified the entire mitochondrial genome by use of 32 pairs of overlapping primers, and to identify the mutations, we sequenced DNA fragments showing different banding patterns between normal and tumor mtDNA. Fourteen of eighteen (77.8%) oral carcinomas displayed somatic mtDNA mutations, with a total of 26 mutations. Among them, six were in the mRNA coding region. Three were missense mutations (C14F, H186R, T173P) in NADH dehydrogenase subunit 2, and one was a frameshift mutation, 9485delC, in cytochrome c oxidase subunit Ill. Eight (44%) tumors had insertion or deletion mutations in the nucleotide position 303-309 poly C region of the D-loop. Multiple large deletions were also observed. Our results demonstrate that somatic mtDNA mutations occur in oral cancer. Some missense and frameshift mutations may play an important role in the tumorigenesis of this carcinoma. More extensive biochemical and molecular studies will be necessary for determining the pathologic effect of these somatic mutations. (C) 2003 Wiley-Liss, Inc.