Hemizygous deletion and hypermethylation of RUNX3 gene in hepatocellular carcinoma

World J Gastroenterol. 2004 Feb 1;10(3):376-80. doi: 10.3748/wjg.v10.i3.376.


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.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Carcinoma, Hepatocellular / genetics*
  • Core Binding Factor Alpha 3 Subunit
  • DNA Methylation*
  • DNA-Binding Proteins / genetics*
  • Gene Deletion*
  • Humans
  • Liver Neoplasms / genetics*
  • Loss of Heterozygosity
  • Middle Aged
  • Transcription Factors / genetics*


  • Core Binding Factor Alpha 3 Subunit
  • DNA-Binding Proteins
  • Runx3 protein, human
  • Transcription Factors