High-resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays

Authors

  • Jeremy A. Squire,

    Corresponding author
    1. Princess Margaret Hospital and The Ontario Cancer Institute, Toronto, Ontario, Canada
    2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    • Ontario Cancer Institute, Division of Cellular and Molecular Biology, 610 University Ave., Room 9-721, Toronto, Ontario M5G 2M9, Canada
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  • Jianming Pei,

    1. Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
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  • Paula Marrano,

    1. Princess Margaret Hospital and The Ontario Cancer Institute, Toronto, Ontario, Canada
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  • Ben Beheshti,

    1. Princess Margaret Hospital and The Ontario Cancer Institute, Toronto, Ontario, Canada
    2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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  • Jane Bayani,

    1. Princess Margaret Hospital and The Ontario Cancer Institute, Toronto, Ontario, Canada
    2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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  • Gloria Lim,

    1. Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
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  • Laura Moldovan,

    1. Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
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  • Maria Zielenska

    1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    2. Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
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Abstract

Conventional cytogenetic and comparative genomic hybridization (CGH) studies have shown that osteosarcomas (OSs) are characterized by complex structural and numerical chromosomal alterations and gene amplification. In this study, we used high-resolution CGH to investigate recurrent patterns of genomic imbalance by use of DNA derived from nine OS tumors hybridized to a 19,200-clone cDNA microarray. In six OSs, there was copy number gain or amplification of 6p, with a minimal region of gain centering on segment 6p12.1. In seven OSs, the pattern of amplification affecting chromosome arm 8q showed high-level gains of 8q12–21.3 and 8q22–q23, with amplification of the MYC oncogene at 8q24.2. Seven OSs showed copy number gain or amplification of 17p between the loci bounded by GAS7 and PMI (17p11.2–17p12), and three of these tumors also showed small losses at 17p13, including the region containing TP53. An in silico analysis of the distribution of segmental duplications (duplicons) in this region identified a large number of tracts consisting of paralogous sequences mapping to the 17p region, encompassing the region of deletions and amplifications in OS. Interestingly, within this same region there were clusters of duplicons and several genes that are expressed during bone morphogenesis and in OS. In summary, microarray CGH analysis of the chromosomal imbalances of OS confirm the overall pattern observed by use of metaphase CGH and provides a more precise refinement of the boundaries of genomic gains and losses that characterize this tumor. © 2003 Wiley-Liss, Inc.

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