Alteration of gene expression in human hepatocellular carcinoma with integrated hepatitis B virus DNA

Akihiro Tamori, Yoshihiro Yamanishi, Shuichi Kawashima, Minoru Kanehisa, Masaru Enomoto, Hiromu Tanaka, Shoji Kubo, Susumu Shiomi, Shuhei Nishiguchi

    Research output: Contribution to journalArticle

    55 Citations (Scopus)

    Abstract

    Purpose: Integration of hepatitis B virus (HBV) DNA into the human genome is one of the most important steps in HBV-related carcinogenesis. This study attempted to find the link between HBV DNA, the adjoining cellular sequence, and altered gene expression in hepatocellular carcinoma (HCC) with integrated HBV DNA. Experimental Design: We examined 15 cases of HCC infected with HBV by cassette ligation - mediated PCR. The human DNA adjacent to the integrated HBV DNA was sequenced. Protein coding sequences were searched for in the human sequence. In five cases with HBV DNA integration, from which good quality RNA was extracted, gene expression was examined by cDNA microarray analysis. Results: The human DNA sequence successive to integrated HBV DNA was determined in the 15 HCCs. Eight protein-coding regions were involved: ras-responsive element binding protein 1, calmodulin 1, mixed lineage leukemia 2 (MLL2), FLJ333655, LOC220272, LOC255345, LOC220220, and LOC168991. The MLL2 gene was expressed in three cases with HBV DNA integrated into exon 3 of MLL2 and in one case with HBV DNA integrated into intron 3 of MLL2. Gene expression analysis suggested that two HCCs with HBV integrated into MLL2 had similar patterns of gene expression compared with three HCCs with HBV integrated into other loci of human chromosomes. Conclusions: HBV DNA was integrated at random sites of human DNA, and the MLL2 gene was one of the targets for integration. Our results suggest that HBV DNA might modulate human genes near integration sites, followed by integration site-specific expression of such genes during hepatocarcinogenesis.

    Original languageEnglish
    Pages (from-to)5821-5826
    Number of pages6
    JournalClinical Cancer Research
    Volume11
    Issue number16
    DOIs
    Publication statusPublished - Aug 15 2005

    Fingerprint

    Hepatitis B virus
    Hepatocellular Carcinoma
    Gene Expression
    DNA
    Leukemia
    Virus Integration
    Genes
    Calmodulin-Binding Proteins
    Human Chromosomes
    Human Genome
    Microarray Analysis
    Oligonucleotide Array Sequence Analysis
    Introns
    Open Reading Frames
    Ligation
    Exons
    Carcinogenesis
    Research Design
    RNA

    All Science Journal Classification (ASJC) codes

    • Oncology
    • Cancer Research

    Cite this

    Tamori, A., Yamanishi, Y., Kawashima, S., Kanehisa, M., Enomoto, M., Tanaka, H., ... Nishiguchi, S. (2005). Alteration of gene expression in human hepatocellular carcinoma with integrated hepatitis B virus DNA. Clinical Cancer Research, 11(16), 5821-5826. https://doi.org/10.1158/1078-0432.CCR-04-2055

    Alteration of gene expression in human hepatocellular carcinoma with integrated hepatitis B virus DNA. / Tamori, Akihiro; Yamanishi, Yoshihiro; Kawashima, Shuichi; Kanehisa, Minoru; Enomoto, Masaru; Tanaka, Hiromu; Kubo, Shoji; Shiomi, Susumu; Nishiguchi, Shuhei.

    In: Clinical Cancer Research, Vol. 11, No. 16, 15.08.2005, p. 5821-5826.

    Research output: Contribution to journalArticle

    Tamori, A, Yamanishi, Y, Kawashima, S, Kanehisa, M, Enomoto, M, Tanaka, H, Kubo, S, Shiomi, S & Nishiguchi, S 2005, 'Alteration of gene expression in human hepatocellular carcinoma with integrated hepatitis B virus DNA', Clinical Cancer Research, vol. 11, no. 16, pp. 5821-5826. https://doi.org/10.1158/1078-0432.CCR-04-2055
    Tamori, Akihiro ; Yamanishi, Yoshihiro ; Kawashima, Shuichi ; Kanehisa, Minoru ; Enomoto, Masaru ; Tanaka, Hiromu ; Kubo, Shoji ; Shiomi, Susumu ; Nishiguchi, Shuhei. / Alteration of gene expression in human hepatocellular carcinoma with integrated hepatitis B virus DNA. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 16. pp. 5821-5826.
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    AU - Kanehisa, Minoru

    AU - Enomoto, Masaru

    AU - Tanaka, Hiromu

    AU - Kubo, Shoji

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