Significance of somatic mutations and content alteration of mitochondrial DNA in esophageal cancer.
Significance of somatic mutations and content alteration of mitochondrial DNA in esophageal cancer.
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DOI：
10.1186/1471-2407-6-93
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发表时间：
2006-04-18
期刊：
影响因子：
3.8
通讯作者：
Wong LJ
中科院分区：
文献类型：
--
作者：
Tan DJ;Chang J;Liu LL;Bai RK;Wang YF;Yeh KT;Wong LJ
线粒体在能量代谢、ROS产生、衰老和细胞凋亡启动中的作用暗示了其在肿瘤发生中的重要性。在这项研究中，我们的目的是建立突变谱，并了解体细胞mtDNA突变在食管癌中的作用。使用时间温度梯度凝胶电泳（TTGE），随后通过直接DNA测序来鉴定突变，在20对（18个食管鳞状细胞癌，一个腺鳞癌和一个腺癌）食管癌的肿瘤/周围正常组织中筛选整个线粒体基因组的体细胞突变。在55%（11/20）的肿瘤中发现了14个线粒体DNA突变，包括ND4L、ATP 6亚基和ND4基因的2个新的错义突变和1个移码突变。9个突变（64%）位于D环区。发现了大量的种系变异，其中至少有10个是新的，5个是错义突变，其中一些发生在进化上保守的结构域。使用实时定量PCR分析，发现mtDNA含量在一些肿瘤中增加，而在另一些肿瘤中减少。分子和其他临床病理结果的分析并未显示体细胞线粒体DNA突变与线粒体DNA含量之间或线粒体DNA含量与转移状态之间存在显着相关性。我们的研究结果表明，体细胞线粒体DNA突变在食管癌是频繁的。某些错义突变和移码突变可能在食管癌的发生中起重要作用。更广泛的生物化学和分子研究将是必要的，以确定这些体细胞突变的病理意义。
The roles of mitochondria in energy metabolism, the generation of ROS, aging, and the initiation of apoptosis have implicated their importance in tumorigenesis. In this study we aim to establish the mutation spectrum and to understand the role of somatic mtDNA mutations in esophageal cancer. The entire mitochondrial genome was screened for somatic mutations in 20 pairs (18 esophageal squamous cell carcinomas, one adenosquamous carcinoma and one adenocarcinoma) of tumor/surrounding normal tissue of esophageal cancers, using temporal temperature gradient gel electrophoresis (TTGE), followed by direct DNA sequencing to identify the mutations. Fourteen somatic mtDNA mutations were identified in 55% (11/20) of tumors analyzed, including 2 novel missense mutations and a frameshift mutation in ND4L, ATP6 subunit, and ND4 genes respectively. Nine mutations (64%) were in the D-loop region. Numerous germline variations were found, at least 10 of them were novel and five were missense mutations, some of them occurred in evolutionarily conserved domains. Using real-time quantitative PCR analysis, the mtDNA content was found to increase in some tumors and decrease in others. Analysis of molecular and other clinicopathological findings does not reveal significant correlation between somatic mtDNA mutations and mtDNA content, or between mtDNA content and metastatic status. Our results demonstrate that somatic mtDNA mutations in esophageal cancers are frequent. Some missense and frameshift mutations may play an important role in the tumorigenesis of esophageal carcinoma. More extensive biochemical and molecular studies will be necessary to determine the pathological significance of these somatic mutations.
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影响因子：
3.7
作者：
Taschner, PEM;Jansen, JC;Devilee, P
通讯作者：
Devilee, P
影响因子：
3.7
作者：
Tan, DJ;Chang, J;Wong, LJC
通讯作者：
Wong, LJC
影响因子：
4.7
作者：
Cuezva, JM;Chen, GA;Beer, DG
通讯作者：
Beer, DG
DOI：
10.1093/jnci/92.21.1753
发表时间：
2000-11-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Mark, SD;Qiao, YL;Taylor, PR
通讯作者：
Taylor, PR
影响因子：
3.7
作者：
Badenhop, RF;Cherian, S;Schofield, PR
通讯作者：
Schofield, PR