Abstract for presentation at 11th International Congress of Human Genetics

Genetic characterization of chordoma using tiling resolution BAC microarrays

  • Dr Karolin Hansén Hallor, Department of Clinical Genetics, Lund University Hospital, Lund, Sweden
  • Dr Markus Heidenbled, Department of Clinical Genetics, Lund University Hospital, Lund, Sweden
  • Dr Johan Staaf, Department of Oncology, Lund University Hospital, Lund, Sweden
  • Dr Göran Jönsson, Department of Oncology, Lund University Hospital, Lund, Sweden
  • Prof Åke Borg, Department of Oncology, Lund University Hospital, Lund, Sweden
  • Prof Nils Mandahl, Department of Clinical Genetics, Lund University Hospital, Lund, Sweden
  • Prof Fredrik Mertens, Department of Clinical Genetics, Lund University Hospital, Lund, Sweden

    • Introduction: Chordoma is a relatively rare neoplasm accounting for 1-4% of all primary malignant bone tumors. Usually located in the axial skeleton, chordomas are believed to be derived from remnants of the embryonal notochord. Most cytogenetically investigated chordomas have displayed near-diploid or moderately hypodiploid karyotypes, with several numerical and structural rearrangements. However, no consistent structural chromosome aberration has been reported. The purpose of this study was to genetically characterize these tumors in detail using tiling resolution BAC microarrays.
    Methods: Genome-wide array comparative genomic hybridization (array CGH) was performed on 12 chordomas using tiling resolution microarrays, encompassing 32,433 BAC clones. Selected copy number gains and losses were confirmed using FISH, also in samples lacking material for array CGH.
    Results: The DNA copy number profiles mainly revealed losses of large chromosomal regions, and no high level amplifications were detected. Loss of chromosomes 3, 10, 18, and 22, as well as of chromosomal arms 1p and 9p, were the most frequent findings. Chromosomal gains were recurrently detected for regions on 7p, distal 12p and distal 12q.
    Conclusion: This study demonstrates that genetic aberrations in chordomas primarily involve chromosomal losses and that high level amplifications are uncommon. The DNA copy number profiles were highly consistent with previous cytogenetic and metaphase-CGH findings. However, many of the DNA copy number changes identified in this study would not have been detected using conventional CGH due to its relatively low resolution. In addition, even though half of the samples analyzed in this study displayed a normal karyotype upon G-banding, array CGH detected chromosomal aberrations in all cases. This is most likely explained by a growth advantage in vitro for normal cell populations. The results thus indicate that all chordomas harbor chromosomal imbalances.

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