Fragile histidine triad gene alterations are not essential for hepatocellular carcinoma development in South Korea

World J Gastroenterol. 2008 Jun 14;14(22):3526-33. doi: 10.3748/wjg.14.3526.

Abstract

Aim: To establish the role of FHIT in the pathogenesis hepatocellular carcinoma (HCC).

Methods: We examined genomic alterations, as well as, mRNA and protein expression patterns from the FHIT gene, in 48 surgically resected hepatocellular carcinoma (HCC) tissues. Additionally, p53 mutations were analyzed.

Results: Aberrant FHIT transcripts were detected in 11 of 48 surrounding non-tumor liver tissues and 27 of 48 HCC samples (22.9% vs 56.3%, P = 0.002). No point mutations were identified within the open reading frame region of FHIT. Loss of heterozygosity (LOH) of the FHIT locus was detected in 4 of 42 informative cases for D3S1300, and 3 of 29 informative cases for D3S1313. Reduced expression of FHIT protein (Fhit) was observed in 8 (16.7%) of 48 HCC samples, with complete loss of Fhit in only 1 case. There were no associations with abnormal transcripts, LOH, and Fhit expression. p53 mutations were identified in 9 of the 48 HCC cases. However, none of the cases displayed a G to T transversion at p53 codon 249.

Conclusion: Aberrant FHIT transcripts were more common in HCC tissues as compared to non-cancerous liver tissues. However, Fhit expression was lost or reduced in a minor fraction of HCC tissues, while it was strongly expressed in non-cancerous liver tissues. Therefore, our study suggests that FHIT plays a role in relatively few HCC cases in South Korea.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Anhydride Hydrolases / genetics*
  • Adult
  • Aged
  • Asian People / genetics
  • Carcinoma, Hepatocellular / ethnology
  • Carcinoma, Hepatocellular / genetics*
  • Case-Control Studies
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Korea
  • Liver Neoplasms / ethnology
  • Liver Neoplasms / genetics*
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neoplasm Proteins / genetics*
  • Polymorphism, Genetic / genetics*
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Neoplasm Proteins
  • Tumor Suppressor Protein p53
  • fragile histidine triad protein
  • Acid Anhydride Hydrolases