The retinoblastoma gene is involved in malignant progression of astrocytomas

Authors

  • Dr John W. Henson MD,

    Corresponding author
    1. Molecular Neuro-Oncology Laboratory, Neurology and Neurosurgical Services and Department of Pathology, Massachusetts General Hospital Boston, MA
    2. Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA
    • Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129
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  • Bernd L. Schnitker BS,

    1. Molecular Neuro-Oncology Laboratory, Neurology and Neurosurgical Services and Department of Pathology, Massachusetts General Hospital Boston, MA
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  • Katia M. Correa BS,

    1. Molecular Neuro-Oncology Laboratory, Neurology and Neurosurgical Services and Department of Pathology, Massachusetts General Hospital Boston, MA
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  • Andreas von Deimling MD,

    1. Institute for Neuropathology, University of Bonn, Bonn, Germany
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  • Frank Fassbender BS,

    1. Institute for Neuropathology, University of Bonn, Bonn, Germany
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  • Hong-Ji Xu MD, PhD,

    1. The Center for Biotechnology, Baylor College of Medicine, The Woodlands, TX
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  • William F. Benedict MD,

    1. The Center for Biotechnology, Baylor College of Medicine, The Woodlands, TX
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  • David W. Yandell PhD,

    1. Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA
    2. Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
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  • Dr David N. Louis MD

    Corresponding author
    1. Molecular Neuro-Oncology Laboratory, Neurology and Neurosurgical Services and Department of Pathology, Massachusetts General Hospital Boston, MA
    2. Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA
    • Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129
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Abstract

Loss of chromosome 13q occurs in up to 50% of human astrocytomas, suggesting the presence of an astrocytoma tumor suppressor gene on that chromosome. To determine whether the retinoblastoma susceptibility gene (Rb) on 13q 14 contributes to the formation of astrocytomas, we examined 85 tumors for loss of heterozygosity (LOH) at the intragenic Rb 1.20 locus. LOH was detercted in 16 of 54 informative high-grade astrocytomas (30%), but was not detected in 12 low-grade gliomas. Deletion mapping with flanking markers on 13q revealed that the Rb 1.20 region was preferentially targeted by the deletions. Tumors with LOH at Rb 1.20 were examined for mutations in the remaining Rb allele using single-strand conformational polymorphism (SSCP) analysis and direct DNA sequencing. Mutations were detected in exon 8 (1 tumor), exon 24 (2 tumors), and intron 24 (1 tumor). Rb protein expression, as assessed by immunohistochemistry, was altered in 3 of 9 cases with LOH and in 1 tumor without LOH. Our results demonstrate that Rb inactivation contributes to the formation of high-grade astrocytomas, and therefore implicate a second, known tumor suppressor gene in astrocytoma tumorigenesis.

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