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


CONCLUSIONS
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.
Department of Surgery, University of Ulsan College of Medicine, Biomedical Research Center, Ulsan University Hospital, Ulsan 682-714, South Korea.
Chang-Woo
CW
Nam
Jung-Woo
JW
Shin
Neung-Hwa
NH
Park
D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007723:Korea; D008113:Liver Neoplasms / Q000208:ethnology / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D000099170:Bis(5'-adenosyl)triphosphatase