Cancer-germline gene expression in pediatric solid tumors using quantitative real-time PCR

Authors

  • Joannes F.M. Jacobs,

    1. Department of Pediatric Hemato-Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • Francis Brasseur,

    1. Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium
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  • Christina A. Hulsbergen-van de Kaa,

    1. Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • Mandy W.M.M. van de Rakt,

    1. Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • Carl G. Figdor,

    1. Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • Gosse J. Adema,

    1. Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • Peter M. Hoogerbrugge,

    1. Department of Pediatric Hemato-Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • Pierre G. Coulie,

    1. Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Brussels, Belgium
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  • I. Jolanda M. de Vries

    Corresponding author
    1. Department of Pediatric Hemato-Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    2. Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    • Department of Tumor Immunology, Radboud University Nijmegen Medical Centre, NCMLS, 278 TIL, Post Box 9101, 6500 HB Nijmegen, The Netherlands
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    • Fax: +31-243540339.


Abstract

Cancer-germline genes (CGGs) code for immunogenic antigens that are present on various human tumors but not on normal tissues. The importance of CGGs in cancer immunotherapy has led to detailed studies of their expression in a range of human tumors. We measured the levels of expression of 12 CGGs in various pediatric solid tumors to identify targets for therapeutic cancer vaccines. Quantitative real-time PCR (qPCR) was used to measure the expression of 8 MAGE genes and of genes LAGE-2/NY-ESO-1 and GAGE-1, 2, 8 in 9 osteosarcomas, 10 neuroblastomas, 12 rhabdomyosarcomas and 18 Ewing's sarcomas. Nine tumors were also examined by immunohistochemistry with monoclonal antibodies specific for the MAGE-A1, MAGE-A4 and NY-ESO-1 proteins. All osteosarcoma and 80% of neuroblastoma samples expressed several CGGs at high levels. Six of 12 rhabdomyosarcomas and 11 of 18 Ewing's sarcomas expressed at least one CGG. Immunohistochemistry data correlated well with qPCR results and showed a homogeneous protein distribution pattern in most positive tumors. No correlation was found between the levels of CGG expression in the tumors and clinicopathological parameters of the patients. Pediatric solid tumors express several CGGs, which encode antigens that could be targeted in therapeutic vaccination trials. Several CGGs of the MAGE, GAGE and LAGE families are coexpressed in a large proportion of osteosarcoma and neuroblastoma samples. Some rhabdomyosarcomas express several of these genes at high levels. Ewing's sarcomas have an overall low CGG expression. © 2006 Wiley-Liss, Inc.

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