• Open Access

Genome-wide array-based comparative genomic hybridization analysis of pancreatic adenocarcinoma: Identification of genetic indicators that predict patient outcome

Authors

  • Panayiotis Loukopoulos,

    1. Pathology Division, and
    Search for more papers by this author
    • 7

      Present address: Pathology Division, Faculty of Veterinary Medicine, Aristotle University, Thessaloniki 54124, Greece.

  • Tatsuhiro Shibata,

    Corresponding author
    1. Pathology Division, and
    2. Cancer Genomics Project, National Cancer Center Research Institute, 51-1, Tsukiji, Chuo-ku, Tokyo 1040-045;
      To whom correspondence should be addressed. E-mail: tashibat@ncc.go.jp
    Search for more papers by this author
  • Hiroto Katoh,

    1. Pathology Division, and
    2. Cancer Genomics Project, National Cancer Center Research Institute, 51-1, Tsukiji, Chuo-ku, Tokyo 1040-045;
    Search for more papers by this author
  • Akiko Kokubu,

    1. Pathology Division, and
    2. Cancer Genomics Project, National Cancer Center Research Institute, 51-1, Tsukiji, Chuo-ku, Tokyo 1040-045;
    Search for more papers by this author
  • Michiie Sakamoto,

    1. Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 1600-016;
    Search for more papers by this author
  • Ken Yamazaki,

    1. Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 1600-016;
    Search for more papers by this author
  • Tomoo Kosuge,

    1. Department of Hepato-Biliary-Pancreatic Surgery, National Cancer Center, Hospital, 51-1, Tsukiji, Chuo-ku, Tokyo 1040-045;
    Search for more papers by this author
  • Yae Kanai,

    1. Pathology Division, and
    Search for more papers by this author
  • Fumie Hosoda,

    1. Cancer Genomics Project, National Cancer Center Research Institute, 51-1, Tsukiji, Chuo-ku, Tokyo 1040-045;
    Search for more papers by this author
  • Issei Imoto,

    1. Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, 15-45 Yushima, Bunkyo-ku, Tokyo 1138-519;
    2. Core Research for Evolutionary Science and Technology (CREST) of the Japan Science and Technology (JST) Corporation, 41-8 Hon-machi Kawaguchi, Saitama 3320-012, Japan
    Search for more papers by this author
  • Misao Ohki,

    1. Cancer Genomics Project, National Cancer Center Research Institute, 51-1, Tsukiji, Chuo-ku, Tokyo 1040-045;
    Search for more papers by this author
  • Jyoji Inazawa,

    1. Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, 15-45 Yushima, Bunkyo-ku, Tokyo 1138-519;
    2. Core Research for Evolutionary Science and Technology (CREST) of the Japan Science and Technology (JST) Corporation, 41-8 Hon-machi Kawaguchi, Saitama 3320-012, Japan
    Search for more papers by this author
  • Setsuo Hirohashi

    1. Pathology Division, and
    Search for more papers by this author

To whom correspondence should be addressed. E-mail: tashibat@ncc.go.jp

Abstract

We analyzed the subchromosomal numerical aberrations of 44 surgically resected pancreatic adenocarcinomas by array-based comparative genomic hybridization. The aberration profile ranged widely between cases, suggesting the presence of multiple or complementary mechanisms of evolution in pancreatic cancer, and was associated with lymph node metastasis and venous or serosal invasion. A large number of small loci, previously uncharacterized in pancreatic cancer, showed non-random loss or gain. Frequent losses at 1p36, 4p16, 7q36, 9q34, 11p15, 11q13, 14q32-33, 16p13, 17p11-13, 17q11-25, 18q21-tel, 19p13, 21q22 and 22q11-12, and gains at 1q25, 2p16, 2q21-37, 3q25, 5p14, 5q11-13, 7q21, 7p22, 8p22, 8q21-23, 10q21, 12p13, 13q22, 15q13-22 and 18q11 were identified. Sixteen loci were amplified recurrently. We identified novel chromosomal alterations that were significantly associated with a range of malignant phenotypes. Gain of LUNX, HCK, E2F1 and DNMT3b at 20q11, loss of p73 at 1p36 and gain of PPM1D at 17q23 independently predicted patient outcome. Expression profiling of amplified genes identified Smurf1 and TRRAP at 7q22.1, BCAS1 at 20q13.2-3, and VCL at 10q22.1 as potential novel oncogenes. Our results contribute to a complete description of genomic structural aberrations and the identification of potential therapeutic targets and genetic indicators that predict patient outcome in pancreatic adenocarcinoma. (Cancer Sci 2007; 98: 392–400)

Ancillary