Mitochondrial D-loop mutations and deletion profiles of cancerous and noncancerous liver tissue in hepatitis B virus-infected liver.

Mitochondrial D-loop mutations and deletion profiles of cancerous and noncancerous liver tissue in hepatitis B virus-infected liver.
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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。

DOI:
10.1038/sj.bjc.6602496
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发表时间:
2005-04-11
影响因子:
8.8
通讯作者:
Harrison, DJ
Harrison, DJ
中科院分区:
医学1区
文献类型:
--
作者:
Wheelhouse, NM;Lai, PBS;Wigmore, SJ;Ross, JA;Harrison, DJ

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世界范围内肝细胞癌(HCC)的最大单一潜在病因是乙型肝炎病毒(HBV)感染。乙型肝炎病毒增加细胞氧化应激,HCC的发生需要很长的潜伏期。该研究旨在确定HBV患者的线粒体DNA异常是否与HCC相关。在目前的研究中,研究人员调查了HBV感染患者肿瘤和匹配正常组织中线粒体基因组特定区域突变和缺失的频率。对照组中携带D-loop突变的比例为11%,显著低于HCC患者的非癌组织(49%,P=0.033)和肿瘤组织(59%,P=0.014)。相比之下,在HCC受试者的对照肝和非癌性肝组织中检测到常见的4977 bp线粒体基因组缺失的病例数(分别为100%和95%)显著高于癌性肝组织(28%,P<0.001)。这些观察结果表明,炎症过程有助于线粒体突变率。然而,癌变组织中较大缺失的频率较低表明,在肝癌发生过程中,要么存在针对含有较大缺失的线粒体的选择,要么存在针对含有这些线粒体的细胞的选择。
The largest single underlying cause of hepatocellular carcinoma (HCC) worldwide is hepatitis B virus (HBV) infection. Hepatitis B virus increases cellular oxidative stress and the development of HCC occurs after a long latency period. The study was carried out to determine whether mitochondrial DNA abnormalities were associated with HCC in individuals with HBV. The frequency of mutation and deletion of specific areas of the mitochondrial genome in tumour and matched normal tissue of patients with HBV infection was investigated in the current study. The percentage of control subjects harbouring D-loop mutations was 11%, which was significantly lower than that observed in both the noncancerous (49%, P=0.033) and tumour tissue (59%, P=0.014) of patients with HCC. In contrast, the number of cases in which the common 4977 bp deletion of the mitochondrial genome was detected was significantly greater in control liver and noncancerous liver tissue of subjects with HCC (100 and 95%, respectively) than in cancerous liver tissue (28%, P<0.001). These observations suggest that the inflammatory process contributes to the rate of mitochondrial mutations. However, the lower frequency of the large deletion in cancerous tissue suggests that there is selection against either mitochondria, which harbour large deletions, or against cells that contain these mitochondria during hepatocarcinogenesis.
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期刊: ONCOGENE
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