摘要
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 condon 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 hepatocellualr carcinogenesis.
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 condon 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 hepatocellualr carcinogenesis.
