Search for novel genomic regions related to liver carcinogenesis by using a hepatitis B virus integration site as a genetic probe

以乙型肝炎病毒整合位点为基因探针寻找与肝癌发生相关的新基因组区域

• 批准号: 18590742
• 负责人: MINAMI Masahito
• 金额: $ 2.43万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590742/
• 关键词: hepatitis B virus; integration; liver carcinogenesis; hTERT; MLL4

Human genomic regions flanking integrated hepatitis B virus (HBV) were investigated from liver tissues of chronic hepatitis, liver cancers and non-cancerous tissues surrounding liver cancers. We developed an HBV-Alu PCR method to efficiently amplify the viral-host junctions. From 26 cases with chronic hepatitis and 10 with liver cancer, 75 viral-host junctions were cloned and genomic sequences were determined. Together with genomic database search and our results, we could identify a human telomerase reverse transcriptase (hTERT) gene and MLL4 gene as common integration sites. These two genes were found integrated exclusively in liver cancer tissues. HBV integration into an hTERT gene was found in about 5 % of liver cancer cases where HBV integration sites were investigated.To investigate when the integration into hTERT occur during chronic HBV infection, we searched for HBV-hTERT chimeric sequences in chronic hepatitis tissues by PCR with several primer sets, but no HBV-hTERT chimeras were detected. Thus it is suggested that HBV integration into the hTERT gene occurs in more advanced stages of HBV infection than chronic hepatitis.

从慢性肝炎、肝癌及癌旁非癌组织中检测整合型B型肝炎病毒（HBV）基因组侧翼区。我们开发了HBV-Alu PCR方法，以有效地扩增病毒-宿主连接。从26例慢性肝炎和10例肝癌中克隆了75个病毒-宿主连接点，并测定了基因组序列。结合基因组数据库检索和我们的结果，我们可以确定一个人端粒酶逆转录酶（hTERT）基因和MLL 4基因作为共同的整合位点。发现这两个基因仅整合在肝癌组织中。在研究HBV整合位点的肝癌病例中，约5%的病例中发现HBV整合到hTERT基因中，为了研究在慢性HBV感染期间何时整合到hTERT基因中，我们使用几种引物对通过PCR在慢性肝炎组织中寻找HBV-hTERT嵌合体序列，但没有检测到HBV-hTERT嵌合体。因此，这表明，HBV整合到hTERT基因发生在更先进的阶段，HBV感染比慢性肝炎。

项目成果

Unusually high incidence of hepatitis B virus integration into the MLL gene in hepatocellular carcinoma.

乙型肝炎病毒整合到肝细胞癌 MLL 基因中的发生率异常高。

• 发表时间: 2006
• 期刊: Clinical Cancer Research 12
• 作者: Minami M;Fujii K;Miyagawa M;Okanoue T
• 通讯作者: Okanoue T

Unusually high incidence of hepatitis B virus integration into the MLL gene in hepatocellular carcinoma

乙型肝炎病毒整合到肝细胞癌 MLL 基因中的发生率异常高

• 发表时间: 2006
• 期刊: Clinical Cancer Research 12(11 Pt 1)
• 作者: Minami;M.;Fujii;K.;Miyagawa;M.;Okanoue;T
• 通讯作者: T

今日の診療のために ガイドライン 外来診療2007, 泉 孝英, 編

当今医疗指南 门诊治疗 2007 年，泉隆秀主编

• 发表时间: 2007
• 作者: Minami;M.;Fujii;K.;Miyagawa;M.;Itoh;Y.;Okanoue;T;南祐 仁
• 通讯作者: 南祐 仁

臨床に直結する肝・胆・膵疾患治療のエビデンス.跡見裕, 上村直実, 白鳥敬子, 正木尚彦, 編集

与临床实践直接相关的肝脏、胆道和胰腺疾病的治疗证据。Hiroshi Atomi、Naomi Uemura、Keiko Shiratori、Naohiko Masaki，编辑。

• 发表时间: 2007
• 作者: 南祐 仁;岡上 武
• 通讯作者: 岡上 武

Umusually high incidence of hepatitis B virus integration into the MLL gene in hepatocellular carcinoma

乙型肝炎病毒整合到肝细胞癌 MLL 基因中的发生率通常很高

• 发表时间: 2006
• 期刊: Clinical Cancer Research 12(11Pt1)
• 作者: Minami M;Fujii K;Miyagawa M;Okanoue T.
• 通讯作者: Okanoue T.