Precore codon 28 stop mutation in hepatitis B virus from patients with hepatocellular carcinoma.
OBJECTIVE
Hepatitis B virus (HBV) with a stop mutation at precore codon 28 (TGG-->TAG, tryptophan-->stop) was investigated to clarify if such a mutant virus might play a role in hepatocarcinogenesis.


METHODS
A total of 73 patients with HBV-related hepatocellular carcinoma were included in this study. Polymerase chain reaction (PCR) was performed in DNA samples extracted from 73 sera to amplify a HBV-DNA segment involving the precore and proximal core regions, and sequences of PCR products were analyzed to see the presence of the mutations at precore codon 28 by a direct sequencing method.


RESULTS
HBV-DNA was detectable in 64 (88%) patients by PCR. The stop mutation at precore codon 28 was identified in 50 of 58 PCR products (86%), in which direct sequencing was performed. Among patients with this mutant HBV, 21/50 (42%) patients were co-infected with wild-type HBV. The mutant virus was found in 23/28 (82%) patients with hepatitis B e antigen (HBeAg) and 27/30 (90%) patients without HBeAg. The mutant HBV alone was found in 10/28 (36%) patients with HBeAg and 19/30 (63%) without HBeAg. Among those patients on whom laparoscopy was performed, 22/24 (92%) with the precore codon 28 stop mutant alone had cirrhosis, compared to 12/19 (63%) co-infected by both the mutant and the wild-type (p < 0.05). The association of this mutant virus with both the presence and absence of HBeAg, and its association with cirrhosis when there is no co-infection with wild-type HBV, suggests an evolving pattern of liver pathology.


CONCLUSIONS
The high prevalence of a stop mutation at precore codon 28 in these patients with hepatocellular carcinoma suggests that HBV with this mutation may contribute to the development of hepatocellular carcinoma.
Park
Y M
YM
National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Kim
B S
BS
Tabor
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D003062:Codon; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation
D003062:Codon