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  • Oncogenomics
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Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide polymorphism arrays

Oncogene volume 25, pages 5581–5590 (2006)Cite this article

Abstract

Genomic amplification of oncogenes and inactivation of suppressor genes are critical in the pathogenesis of human cancer. To identify chromosomal alterations associated with hepatocarcinogenesis, we performed allelic gene dosage analysis on 36 hepatocellular carcinomas (HCCs). Data from high-density single-nucleotide polymorphism arrays were analysed using the Genome Imbalance Map (GIM) algorithm, which simultaneously detects DNA copy number alterations and loss of heterozygosity (LOH) events. Genome Imbalance Map analysis identified allelic imbalance regions, including uniparental disomy, and predicted the coexistence of a heterozygous population of cancer cells. We observed that gains of 1q, 5p, 5q, 6p, 7q, 8q, 17q and 20q, and LOH of 1p, 4q, 6q, 8p, 10q, 13q, 16p, 16q and 17p were significantly associated with HCC. On 6q24–25, which contains imprinting gene clusters, we observed reduced levels of PLAGL1 expression owing to loss of the unmethylated allele. Finally, we integrated the copy number data with gene expression intensity, and found that genome dosage is correlated with alteration in gene expression. These observations indicated that high-resolution GIM analysis can accurately determine the localizations of genomic regions with allelic imbalance, and when integrated with epigenetic information, a mechanistic basis for inactivation of a tumor suppressor gene in HCC was elucidated.

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Acknowledgements

We thank Hiroko Meguro, Kunihiro Nishimura, Akira Watanabe, Kimihiro Yamashita, Megumi Ihara and Kiyoko Nagura for valuable technical assistance, and Panda Binaya for helpful discussion. This work was supported in part by a Grant-in-Aid for Scientific Research (S) 16101006 (HA) and (C) 17591378 (YM), Scientific Research on Priority Areas 17015008 (HA) and 17015017 (HS), and Special Coordination Fund for Science and Technology from The Ministry of Education, Science, Sports and Culture, and CREST, JST (HA), Mitsui Life Social Welfare Foundation (YM), Smoking Research Foundation (HS), the Program of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO) and Focus 21 Project of New Energy and Industrial Technology Development Organization (NEDO).

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Author notes

  1. Y Midorikawa and S Yamamoto: These contributed equally to this work.

Authors and Affiliations

  1. Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan

    Y Midorikawa, S Yamamoto, S Ishikawa, N Kamimura & H Aburatani

  2. 1st Department of Pathology, Hamamatsu University School of Medicine, Shizuoka, Japan

    H Igarashi & H Sugimura

  3. Hepato-Biliary-Pancreatic Surgery Division, The University of Tokyo, Tokyo, Japan

    Y Midorikawa & M Makuuchi

  4. Core Research for Evolutional Research and Technology,

    H Aburatani

  5. Japan Science and Technology agency, Saitama, Japan

    H Aburatani

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  1. Y Midorikawa
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  2. S Yamamoto
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  3. S Ishikawa
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  4. N Kamimura
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  5. H Igarashi
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  6. H Sugimura
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Correspondence to H Aburatani.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Midorikawa, Y., Yamamoto, S., Ishikawa, S. et al. Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide polymorphism arrays. Oncogene 25, 5581–5590 (2006). https://doi.org/10.1038/sj.onc.1209537

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