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Integration of hepatiti's B virus DNA into the myeloid/lymphoid or mixed-lineage leukemia (MLL4) gene and rearrangements of MLL4 in human hepatocellular carcinoma
被引:94
作者:

Saigo, Kenichi
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机构: Univ Tokyo, Inst Med Sci, Div Genet Diag, Tokyo, Japan

Yoshida, Kenichi
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机构:
Univ Tokyo, Inst Med Sci, Div Genet Diag, Tokyo, Japan Univ Tokyo, Inst Med Sci, Div Genet Diag, Tokyo, Japan

Ikeda, Ryuji
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Univ Tokyo, Inst Med Sci, Div Genet Diag, Tokyo, Japan Univ Tokyo, Inst Med Sci, Div Genet Diag, Tokyo, Japan

Sakamoto, Yoshiko
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机构:
Univ Tokyo, Inst Med Sci, Div Genet Diag, Tokyo, Japan Univ Tokyo, Inst Med Sci, Div Genet Diag, Tokyo, Japan

Murakami, Yoshiki
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机构:
Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan Univ Tokyo, Inst Med Sci, Div Genet Diag, Tokyo, Japan

Urashima, Tetsuro
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机构: Univ Tokyo, Inst Med Sci, Div Genet Diag, Tokyo, Japan

Asano, Takehide
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机构:
Teikyo Univ, Sch Med, Tokyo 173, Japan Univ Tokyo, Inst Med Sci, Div Genet Diag, Tokyo, Japan

Kenmochi, Takashi
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机构: Univ Tokyo, Inst Med Sci, Div Genet Diag, Tokyo, Japan

Inoue, Ituro
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h-index: 0
机构:
Univ Tokyo, Inst Med Sci, Div Genet Diag, Tokyo, Japan
Tokai Univ, Sch Med, Div Mol Life Sci, Kanagawa 2591100, Japan Univ Tokyo, Inst Med Sci, Div Genet Diag, Tokyo, Japan
机构:
[1] Univ Tokyo, Inst Med Sci, Div Genet Diag, Tokyo, Japan
[2] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan
[3] Teikyo Univ, Sch Med, Tokyo 173, Japan
[4] Tokai Univ, Sch Med, Div Mol Life Sci, Kanagawa 2591100, Japan
关键词:
hepatocellular carcinoma;
DNA integration;
hepatitis B virus;
HBx;
MLL4;
D O I:
10.1002/humu.20701
中图分类号:
Q3 [遗传学];
学科分类号:
071007 ;
090102 ;
摘要:
Integration of hepatitis B virus (HBV) DNA into host DNA is detected in about 90% of HBV-related hepatocellular carcinoma (HCC), but the preferential sites of the viral integration etiologically relevant to oncogenesis have been controversial. By using an adaptor-ligation/suppression-PCR, we identified four integrations into the myeloid/lymphoid or mixed-lineage leukemia 4 (MLL4) gene from 10 HCC patients with positive HBV surface antigen (HBsAg). Determination of the cellular-virus DNA junction demonstrated that various lengths of the virus were integrated within 300bp of intron 3 flanked by the Alu element of MLL4. Chimeric hepatitis B virus X gene (HBx)/MLL4 transcripts and the HBx fusion proteins were detected. DNA microarray revealed that HBx/MLL4 fusion proteins suppressed unique genes in HepG2 cells. Finally, chromosomal translocations of intron 3 of MLL4 to the specific region of chromosome 17p11.2 in 22 out of 32 HCC patients were observed, showing that the intron 3 region of MLL4 gene would be a target of translocation breakpoint. In conclusion, the present data suggest that the translocation breakpoint of MLL4 gene is one of the preferential targets for HBV DNA integration into the MLL4 gene and the HBV DNA integration may be involved in liver oncogenesis.
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页码:703 / 708
页数:6
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