Hemizygous deletion and hypermethylation of RUNX3 gene in hepatocellular carcinoma.
OBJECTIVE
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.


CONCLUSIONS
Our findings indicate that inactivation of RUNX3 gene through allelic loss and promoter hypermethylation might be one of the major mechanisms in hepatocellular carcinogenesis.
Xiao
Wen-Hua
WH
Department of Oncology, 304th Hospital of PLA, Beijing 100037, China. w_hxiao@hotmail.com
Liu
Wei-Wen
WW
D000328:Adult; D000368:Aged; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D050677:Core Binding Factor Alpha 3 Subunit; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D008875:Middle Aged; D014157:Transcription Factors / Q000235:genetics*
D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; C493729:Runx3 protein, human; D014157:Transcription Factors