• Open Access

Identification of SMURF1 as a possible target for 7q21.3-22.1 amplification detected in a pancreatic cancer cell line by in-house array-based comparative genomic hybridization

Authors

  • Ayako Suzuki,

    1. Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science,
    2. Department of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho Shinjuku-ku, Tokyo 162-8666;
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  • Tatsuhiro Shibata,

    1. Pathology Division and
    2. Cancer Genomics Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045;
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  • Yutaka Shimada,

    1. First Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8131;
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  • Yoshinori Murakami,

    1. Division of Molecular Pathology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shiroganedai Minato-ku, Tokyo 108-8639;
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  • Akira Horii,

    1. Department of Molecular Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi Aoba-ku, Sendai Miyagi, 980-8575;
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  • Keiko Shiratori,

    1. Department of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho Shinjuku-ku, Tokyo 162-8666;
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  • Setsuo Hirohashi,

    1. Pathology Division and
    2. Cancer Genomics Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045;
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  • Johji Inazawa,

    1. Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science,
    2. Hard Tissue Genome Research Center, and
    3. 21st Century Center of Excellence Program for Molecular Destruction and Reconstitution of Tooth and Bone, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo 113-8510;
    4. Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation, 4-1-8 Hon-machi Kawaguchi, Saitama, 332-0012 Japan
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  • Issei Imoto

    Corresponding author
    1. Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science,
    2. Hard Tissue Genome Research Center, and
    3. Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation, 4-1-8 Hon-machi Kawaguchi, Saitama, 332-0012 Japan
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To whom correspondence should be addressed. E-mail: issecgen@mri.tmd.ac.jp

Abstract

Pancreatic cancer (PC) cell lines provide a useful starting point for the discovery and functional analysis of genes driving the genesis and progression of this lethal cancer. To increase our understanding of the gene copy number changes in pancreatic carcinomas and to identify key amplification and deletion targets, we applied genome-wide array-based comparative genomic hybridization using in-house array (MCG Cancer Array-800) to 24 PC cell lines. Overall, the analyses revealed high genomic complexity, with several copy number changes detected in each line. Homozygous deletions (log2ratio < –2) of eight genes (clones) were seen in 14 of the 24 cell lines, whereas high-level amplifications (log2ratio > 2) of 10 genes (clones) were detected in seven lines. Among them, we focused on high-level amplification at 7q22.1, because target genes for this alteration remain unknown. Through precise mapping of the altered region by fluorescence in situ hybridization, determination of the expression status of genes located within those regions, and functional analysis using knockdown of the gene expression or the ectopic overexpression approach in PC cell lines, as well as immunohistochemical analyses of candidates in primary tumors of PC, we successfully identified SMURF1 as having the greatest potential as a 7q21.3-22.1 amplification target. SMURF1 may work as a growth-promoting gene in PC through overexpression and might be a good candidate as a therapeutic target. Our results suggest that array-based comparative genomic hybridization analysis combined with further genetic and functional examinations is a useful approach for identifying novel tumor-associated genes involved in the pathogenesis of this lethal disease. (Cancer Sci 2008; 99: 986–994)

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