[肝细胞癌中RUNX3基因甲基化与杂合性缺失分析及其临床意义]
[Analysis of methylation and loss of heterozygosity of RUNX3 gene in hepatocellular carcinoma and its clinical significance].
作者信息
Xiao Wen-hua, Liu Wei-wen
机构信息
Department of Oncology, 304 Hospital of PLA, Beijing 100037, China.
出版信息
Zhonghua Gan Zang Bing Za Zhi. 2004 Apr;12(4):227-30.
OBJECTIVE
In order to elucidate role of RUNX3 gene in hepatocarcinogenesis, we detected genetic and epigenetic alteration of RUNX3 gene in hepatocellular carcinoma (HCC).
METHODS
PCR-SSCP, analysis of loss of heterozygosity (LOH), sequencing and methylation-specific PCR (MSP) were used to detect mutation, LOH and DNA methylation of RUNX3 gene in 90 HCCs.
RESULTS
No mutation was found, but three single-nucleotide polymorphisms (SNP) were found and distributed over exon1 and exon4. 30.6% (11/36) of cases showed LOH; 54.4% (49/90) of cases was in hypermethylation. There is a significant correlation between LOH and major portal vein invasive or micro vessel invasion or intrahepatic metastasis.
CONCLUSION
High frequent hypermethylation and LOH of RUNX3 gene were found in HCC. Aberrant RUNX3 gene may play an important role in the development of HCC.
目的
为阐明RUNX3基因在肝癌发生中的作用，我们检测了肝细胞癌（HCC）中RUNX3基因的遗传和表观遗传改变。
方法
采用聚合酶链反应-单链构象多态性分析（PCR-SSCP）、杂合性缺失（LOH）分析、测序及甲基化特异性PCR（MSP）检测90例肝癌中RUNX3基因的突变、LOH及DNA甲基化情况。
结果
未发现突变，但发现3个单核苷酸多态性（SNP），分布于外显子1和外显子4。30.6%（11/36）的病例显示LOH；54.4%（49/90）的病例呈高甲基化。LOH与门静脉主干侵犯、微血管侵犯或肝内转移之间存在显著相关性。
结论
在肝癌中发现RUNX3基因高频率的高甲基化和LOH。RUNX3基因异常可能在肝癌发生中起重要作用。
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