Mitochondrial mutations in hepatocellular carcinomas and fibrolamellar carcinomas.
Mitochondrial mutations in hepatocellular carcinomas and fibrolamellar carcinomas.
复制标题
DOI：
10.1038/modpathol.2010.51
复制
发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
线粒体突变在肝细胞癌中有很好的文献记载，但它们在肿瘤发生中的作用尚不清楚。为了阐明它们的意义，我们对24例肝细胞癌进行了全面的分析，包括量化总线粒体DNA水平，定量具有共同缺失的线粒体DNA水平，以及线粒体控制区的完整测序。此外，通过对纤维板层癌(N=15)的分析，这些研究得到了扩展和加强，纤维板层癌是一种独特的肝癌类型，在电子显微镜下线粒体数量增加。总体而言，大约50%的肝细胞癌的总线粒体DNA水平低于配对的非肿瘤组织。有趣的是，尽管线粒体数量增加，但原发性纤维板层癌的总线粒体DNA水平较低。相比之下，转移性纤维板层癌大大增加了线粒体DNA水平。总体而言，在典型的肝细胞癌中，控制区的缺失与较低的总DNA水平有关，但体细胞单碱基对突变与此无关。事实上，几乎所有的单碱基对突变要么是野生型序列的逆转，要么是已知的群体多态，这强烈表明它们不是直接致癌的。纤维板层癌的线粒体全基因组测序发现了几个体细胞突变，但没有发现一致的突变模式。总体而言，在线粒体DNA总量较低的组织中，共同缺失的水平最高。总之，控制区的缺失，而不是体细胞突变，可能会影响总DNA拷贝数。肝细胞癌的体细胞控制区突变不是直接致癌的，而可能是适应性的。
Mitochondrial mutations are well documented in hepatocellular carcinoma, but their role in carcinogenesis remains unclear. To clarify their significance, a comprehensive analysis was performed of hepatocellular carcinomas (N=24), including quantifying the total mitochondrial DNA levels, quantifying the levels of mitochondrial DNA with the common deletion, and complete sequencing of the mitochondrial control region. In addition, these studies were expanded and reinforced by analysis of fibrolamellar carcinomas (N=15), a unique type of liver carcinoma that has increased numbers of mitochondria on electron microscopy. Overall, approximately 50% of hepatocellular carcinomas had lower levels of total mitochondrial DNA than paired non-neoplastic tissues. Interestingly, despite their increased numbers of mitochondria, primary fibrolamellar carcinomas had lower levels of total mitochondrial DNA. In contrast, metastatic fibrolamellar carcinomas had greatly increased mitochondrial DNA levels. Overall, deletions in the control region were associated with lower total DNA levels in typical hepatocellular carcinoma, but somatic single base pair mutations were not. In fact, almost all single base pair mutations were either reversions to the wild type sequence or known population polymorphisms, strongly suggesting they are not directly oncogenic. Complete sequencing of the entire mitochondrial genome in fibrolamellar carcinomas identified several somatic mutations but no consistent pattern of mutations was found. Overall, the levels of the common deletion were highest in tissues with lower total mitochondrial DNA. In conclusion, control region deletions but not somatic mutations, may influence total DNA copy numbers. Somatic control region mutations in hepatocellular carcinoma are not directly oncogenic but instead may be adaptive.
登录
查看更多内容
影响因子：
14.5
作者：
Mathupala SP;Ko YH;Pedersen PL
通讯作者：
Pedersen PL
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
3.8
作者：
Yamada, S;Nomoto, S;Nakao, A
通讯作者：
Nakao, A
DOI：
10.1016/j.bbrc.2007.07.175
发表时间：
2007-10-12
影响因子：
3.1
作者：
Onishi, Mariko;Sokuza, Yui;Tsujiuchi, Toshifumi
通讯作者：
Tsujiuchi, Toshifumi
肝炎病毒感染的肝脏中癌性和非癌性肝组织的线粒体D环突变和缺失概况。
影响因子：
8.8
作者：
Wheelhouse, NM;Lai, PBS;Wigmore, SJ;Ross, JA;Harrison, DJ
通讯作者：
Harrison, DJ