Stepwise accumulation of distinct genomic aberrations in a patient with progressively metastasizing ependymoma

Authors

  • Till Milde,

    Corresponding author
    1. Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center, Heidelberg, Germany
    • Clinical Cooperation Unit Pediatric Oncology G340, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
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  • Stefan Pfister,

    1. Division of Molecular Genetics (B060), German Cancer Research Center, Heidelberg, Germany
    2. Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany
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  • Andrey Korshunov,

    1. Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany
    2. Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center, Heidelberg, Germany
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  • Hedwig E. Deubzer,

    1. Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center, Heidelberg, Germany
    2. Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany
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  • Ina Oehme,

    1. Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center, Heidelberg, Germany
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  • Aurélie Ernst,

    1. Division of Molecular Genetics (B060), German Cancer Research Center, Heidelberg, Germany
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  • Anna Starzinski-Powitz,

    1. Institute for Cell Biology and Neuroscience, Goethe University Frankfurt, Frankfurt, Germany
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  • Angelika Seitz,

    1. Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany
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  • Peter Lichter,

    1. Division of Molecular Genetics (B060), German Cancer Research Center, Heidelberg, Germany
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  • Andreas von Deimling,

    1. Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany
    2. Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center, Heidelberg, Germany
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  • Olaf Witt

    1. Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center, Heidelberg, Germany
    2. Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany
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Abstract

Nonresectable ependymomas are associated with poor prognosis despite intensive radiochemotherapy and radiation. The molecular pathogenesis of ependymoma initiation and progression is largely unknown. We here present a case of therapy-refractory, progressive ependymoma with cerebrospinal as well as extraneural metastases, which allowed us for the first time to follow the stepwise accumulation of chromosome aberrations during disease progression. Genome-wide DNA copy-number analysis showed sequential deletions on chromosomes 1, 9, and 14 as well as a homozygous deletion of the CDKN2A locus, underscoring its role in tumor progression. Gradual loss at 1p36 was associated with loss of protein expression of the putative tumor suppressor gene AJAP1/SHREW1. In summary, this is the first report on acquired genomic aberrations in ependymoma over time pointing to novel candidate tumor suppressor genes. This analysis provides molecular insights into the chronology of genetic events in this case from initial localized tumor to widespread metastasized disease. © 2008 Wiley-Liss, Inc.

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