Open AccessAnalysis of the complete hepatitis B virus genome in patients with genotype C chronic hepatitis and hepatocellular carcinoma
Author(s) -
Zhang Kai Yu,
Imazeki Fumio,
Fukai Kenichi,
Arai Makoto,
Kanda Tatsuo,
Mikata Rintaro,
Yokosuka Osamu
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00609.x
Subject(s) - hepatocellular carcinoma , genotype , hepatitis b virus , virology , promoter , liver cancer , hepatitis c virus , genome , biology , hepatitis b , medicine , virus , gene , cancer research , genetics , gene expression
Hepatitis B virus (HBV) genotype C and the basic core promoter (BCP) mutations were reported to be associated with the development of hepatocellular carcinoma (HCC). In this study the full sequences of HBV genomes were analyzed in order to find the other predictors of HCC development. We determined the full sequences of HBV genomes in 24 genotype C carriers who developed HCC (HCC group) at the beginning of follow‐up and at the time of HCC diagnosis, and 20 patients who did not develop HCC (non‐HCC group) served as a control. The number of nucleotide and amino acid substitutions in most regions was higher in the HCC group than in the non‐HCC group, and the following substitutions and deletions were found more frequently in the HCC group than in the non‐HCC group: G1317A and T1341C/A/G in the X promoter region were detected in 13 and six of the HCC cases, four and none of the non‐HCC cases, respectively; and pre‐S2 deletion was detected in eight HCC and none of the non‐HCC cases. Compared with the wild type X promoter, the mutant type X promoters, M1 (G1317A), M2 (T1341C), and M4 (T1341G) showed increases in activity of 2.3, 3.8, and 1.4 times, respectively, in HepG2 cells. Substitutions and deletion of nucleotides of the HBV genome, especially the pre‐S2 deletion and G1317A and T1341C/A/G mutations may be useful markers for predicting the development of HCC. ( Cancer Sci 2007; 98: 1921–1929)