Correlation between clinical characteristics and mitochondrial D-loop DNA mutations in hepatocellular carcinoma
Correlation between clinical characteristics and mitochondrial D-loop DNA mutations in hepatocellular carcinoma
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DOI：
10.1007/s00535-004-1445-3
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发表时间：
2004-11-01
影响因子：
6.3
通讯作者：
Inoue, M
中科院分区：
文献类型：
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作者：
Tamori, A;Nishiguchi, S;Inoue, M
背景线粒体DNA(MtDNA)突变存在于多种人类肿瘤中。本研究的目的是评估肝线粒体DNA突变与人肝癌发生的关系。方法：研究方法。对54例肝细胞癌及47例癌旁肝组织和5例转移性肝肿瘤患者的5例非炎症性肝组织标本进行了线粒体DNA直接测序。我们还检测了54例肝癌中的p53突变，以检验核DNA突变和mtDNA突变之间的相关性。结果。在肝细胞癌和非癌肝组织中均发现D-loop区mtDNA突变。在无慢性炎症的正常肝脏中，未检测到线粒体DNA突变。在每个病例中，肝细胞癌中线粒体DNA突变的数量与非癌肝组织中的突变数量相关。MtDNA D-loop区52个突变位点中有12个为肝细胞癌所特有。高分化组mtDNA突变平均数为1.7个，中分化组为4.5个，低分化组为4.6个。因此，在分化较低的肝癌中，mtDNA突变的频率更高。我们在54例肝癌中检测到15例(28%)P53基因突变。P53突变组和野生型p53突变组mtDNA平均突变数分别为5.3%和3.8%(P=0.024)。结论。在分化程度较低的肝癌中发现mtDNA突变的频率较高，也有可能mtDNA突变与肝细胞癌的核DNA突变有关。线粒体DNA突变的积累是预测肝癌发生的有用指标。
Background Mitochondrial DNA (mtDNA) mutations are found in many kinds of human cancer. The aim of this study was to evaluate the relationship between mtDNA mutations in the liver and human hepatocarcinogenesis. Methods. Direct sequencing of mtDNA was done in 54 hepatocellular carcinomas (HCCs) and 47 surrounding liver tissue samples, obtained from 54 patients with HCC, and in 5 liver samples without inflammation, obtained from 5 patients with metastatic liver tumors. We also examined p53 mutations in the 54 HCCs to examine the correlation between nuclear DNA mutations and mtDNA mutations. Results. Mutations of mtDNA in the D-loop region were found in both HCC and noncancerous liver tissue. In normal liver without chronic inflammation, no mtDNA mutation was detected. In every case, the number of mtDNA mutations in HCC correlated with that in noncancerous liver tissue. Twelve of 52 mutation sites in the D-loop region of mtDNA were specific for HCC. The mean number of mtDNA mutations was 1.7 in well-differentiated HCC, as compared with 4.5 in moderately differentiated HCC and 4.6 in poorly differentiated HCC. The frequency of mtDNA mutations was thus higher in less differentiated HCC. We detected p53 mutations in 15 (28%) of 54 HCCs. The mean number of mtDNA mutations was 5.3 in HCC with p53 mutations and 3.8 in HCC with wild-type p53 (P = 0.024). Conclusions. A higher frequency of mtDNA mutations was found in less differentiated HCCs, and it is also possible that mtDNA mutations are related to nuclear DNA mutations in HCC. The accumulation of mtDNA mutations is a useful predictor of hepatocarcinogenesis.