Abstract
To investigate the role of mutant hepatitis B virus (HBV) in the development of
hepatocellular carcinoma (HCC), 20 patients with HCC were studied for precore
and core promoter mutations in tumorous and nontumorous tissues. The precore and
core promoter region was amplified and analyzed by direct sequencing. Among the
20 tumorous and nontumorous tissues, precore mutant HBV was found in 12 (60%)
and 18 (90%), respectively. Of the 12 tumorous tissues with precore mutant, nine
tissues had a single mutation (1896) and one tissue had another single mutation
(1899). The remaining two tissues had a double mutation (1896 and 1899). A
single mutation (1896) and a single mutation (1899) were found in 11 and two of
the 18 nontumorous tissues with precore mutant, respectively. Among 20 tumorous
and nontumorous tissues, HBV with a C to T mutation at nucleotide (nt) 1846 was
detected in six and eight, respectively, and was associated with the virus
carrying a mutation (1896 or 1899) except in two tumorous tissues. Mutations at
nt 1762 and 1764 in core promoter were observed in 16 (80%) tumorous tissues and
18 (90%) nontumorous tissues. Mutations in the precore and core promoter region
were found frequently in nontumorous tissue and in tumorous tissue (18/20 and
12/20 in precore region, 18/20 and 16/20 in core promoter respectively). The
high prevalence of precore and core promoter mutations in liver tissue from
patients with HCC suggests that these mutations may contribute to the
development of HCC.