肝细胞癌中RUNX3基因的半合子缺失和高甲基化
Hemizygous deletion and hypermethylation of RUNX3 gene in hepatocellular carcinoma.
作者信息
Xiao Wen-Hua, Liu Wei-Wen
机构信息
Department of Oncology, 304th Hospital of PLA, Beijing 100037, China.
出版信息
World J Gastroenterol. 2004 Feb 1;10(3):376-80. doi: 10.3748/wjg.v10.i3.376.
Abstract
AIM
To analyze the genetic and epigenetic alterations of RUNX3 gene, a potential putative tumor suppressor gene, in hepatocellular carcinoma (HCC).
METHODS
PCR-based loss of heterozygosity (LOH) detection, analysis of mutation with PCR-single strand conformational polymorphism (SSCP) and sequencing, and methylation study with methylation specific PCR (MSP) were performed on RUNX3 gene in a series of 62 HCCs along with their matched normal tissues.
RESULTS
Mutation of RUNX3 gene was not found, but one single nucleotide polymorphism with T to A transversion at the second nucleotide of the 18th codon was found. Nine of 26 informative cases (34.6%) showed allelic loss on the polymorphic site and 30 cases (48.4%) revealed hypermethylation of RUNX3 gene in promoter CpG islands. Furthermore, of the 9 cases with LOH, 8 (88.9%) also had hypermethylation.
CONCLUSION
Our findings indicate that inactivation of RUNX3 gene through allelic loss and promoter hypermethylation might be one of the major mechanisms in hepatocellular carcinogenesis.
摘要
目的
分析潜在的假定肿瘤抑制基因RUNX3在肝细胞癌（HCC）中的遗传和表观遗传改变。
方法
对62例HCC及其配对的正常组织中的RUNX3基因进行基于聚合酶链反应（PCR）的杂合性缺失（LOH）检测、采用PCR-单链构象多态性（SSCP）和测序分析突变，以及采用甲基化特异性PCR（MSP）进行甲基化研究。
结果
未发现RUNX3基因突变，但在第18密码子的第二个核苷酸处发现了一个由T到A颠换的单核苷酸多态性。26例信息性病例中有9例（34.6%）在多态性位点显示等位基因缺失，30例（48.4%）显示RUNX3基因启动子CpG岛存在高甲基化。此外，在9例存在LOH的病例中，有8例（88.9%）也存在高甲基化。
结论
我们的研究结果表明，通过等位基因缺失和启动子高甲基化使RUNX3基因失活可能是肝细胞癌发生的主要机制之一。
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