Wen-Hua Xiao1, Wei-Wen Liu. 1. Department of Oncology, 304th Hospital of PLA, Beijing 100037, China. w_hxiao@hotmail.com
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.
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.
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