Analysis of the precore and core promoter DNA sequence in liver tissues from patients with hepatocellular carcinoma.

Analysis of the precore and core promoter DNA sequence in liver tissues from patients with hepatocellular carcinoma.
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DOI:
10.3346/jkms.1999.14.4.424
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发表时间:
1999-08
影响因子:
4.5
通讯作者:
Kim HJ
Kim HJ
中科院分区:
医学4区
文献类型:
--
作者:
Cho SW;Shin YJ;Hahm KB;Jin JH;Kim YS;Kim JH;Kim HJ

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为了研究突变型乙型肝炎病毒(HBV)在肝细胞癌(HCC)发展中的作用,我们对20例HCC患者的肿瘤和非肿瘤组织的前启动子和核心启动子突变进行了研究。前核启动子区和核心启动子区通过直接测序扩增和分析。在20例肿瘤组织和非肿瘤组织中,分别有12例(60%)和18例(90%)发现HBV前突变体。在12个前体细胞突变的肿瘤组织中,9个组织有单一突变(1896年),1个组织有另一个单一突变(1899年)。其余两个组织有双重突变(1896年和1899年)。单个突变(1896)和单个突变(1899)分别在11个和2个具有前突变的18个非肿瘤组织中被发现。在20个肿瘤和非肿瘤组织中,分别在6个和8个组织中检测到核苷酸(nt) 1846发生C到T突变的HBV,除了两个肿瘤组织外,与携带突变的病毒(1896或1899)相关。在16例(80%)肿瘤组织和18例(90%)非肿瘤组织中观察到核心启动子nt 1762和1764突变。在非肿瘤组织和肿瘤组织中经常发现前孔和核心启动子区域的突变(前孔区域分别为18/20和12/20,核心启动子分别为18/20和16/20)。HCC患者肝组织中前核启动子和核心启动子突变的高流行率表明,这些突变可能有助于HCC的发展。
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.
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