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LSAMP, a novel candidate tumor suppressor gene in human osteosarcomas, identified by array comparative genomic hybridization

Authors

  • Stine H. Kresse,

    1. Department of Tumor Biology, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway
    2. Faculty Division The Norwegian Radium Hospital, Faculty of Medicine, University of Oslo, Oslo, Norway
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  • Hege O. Ohnstad,

    1. Department of Tumor Biology, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway
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  • Erik B. Paulsen,

    1. Department of Tumor Biology, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway
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  • Bodil Bjerkehagen,

    1. Pathology Clinic, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway
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  • Karoly Szuhai,

    1. Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
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  • Massimo Serra,

    1. Laboratorio di Ricerca Oncologica, Istituto Ortopedico Rizzoli, Bologna, Italy
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  • Karl-Ludwig Schaefer,

    1. Institute of Pathology, Heinrich-Heine University, Düsseldorf, Germany
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  • Ola Myklebost,

    1. Department of Tumor Biology, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway
    2. Norwegian Microarray Consortium, Department of Molecular Biosciences, University of Oslo, Oslo, Norway
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  • Leonardo A. Meza-Zepeda

    Corresponding author
    1. Department of Tumor Biology, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway
    2. Norwegian Microarray Consortium, Department of Molecular Biosciences, University of Oslo, Oslo, Norway
    • Department of Tumor Biology, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo N-0310, Norway
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Abstract

Osteosarcomas are the most common primary malignant tumor of bone, and almost all conventional osteosarcomas are high-grade tumors with complex karyotypes. We have examined DNA copy number changes in 36 osteosarcoma tumors and 20 cell lines using microarray-based comparative genomic hybridization. The most frequent minimal recurrent regions of gain identified in the tumor samples were in 1q21.2-q21.3 (78% of the samples), 1q21.3-q22 (78%), and 8q22.1 (72%). Minimal recurrent regions in 10q22.1-q22.2 (81%), 6q16.1 (67%), 13q14.2 (67%), and 13q21.1 (67%) were most frequently lost. A small region in 3q13.31 (2.1 Mb) containing the gene limbic system-associated membrane protein (LSAMP) was frequently deleted (56%). LSAMP has previously been reported to be a candidate tumor suppressor gene in other cancer types. The deletion was validated using fluorescence in situ hybridization, and the expression level and promoter methylation status of LSAMP were investigated using quantitative real-time reverse transcription PCR and methylation-specific PCR, respectively. LSAMP showed low expression compared to two normal bone samples in 6/15 tumors and 5/9 cell lines with deletion of 3q13.31, and also in 5/14 tumors and 3/11 cell lines with normal copy number or gain. Partial or full methylation of the investigated CpG island was identified in 3/30 tumors and 7/20 cell lines. Statistical analyses revealed that loss of 11p15.4-p15.3 and low expression of LSAMP (both P = 0.011) were significantly associated with poor survival. Our results show that LSAMP is a novel candidate tumor suppressor gene in osteosarcomas. © 2009 Wiley-Liss, Inc.

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