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Genetic characterization of gliomas arising in patients with multiple sclerosis

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Abstract

The co-occurrence of gliomas and multiple sclerosis (MS) in the same patient is uncommon, but a well-reported phenomenon. Most have been high grade astrocytic tumors that developed after the diagnosis of MS, leading authors to postulate that chronic gliosis in demyelinative plaques might be the underlying substrate for secondary induction of a glial neoplasm. Until recently, however, genetic tools have not been available to test the hypothesis that high grade gliomas might arise from longstanding chronic gliosis, with transformation to low grade glioma, and eventually GBM, i.e., be secondary GBMs. We searched our surgical neuropathology and MS Brain Bank databases over the past 25 years (1987–2011) and identified eight cases of co-occurring MS and glioma. After careful review to guarantee both diagnoses, cases were studied by fluorescence in situ hybridization for genetic markers appropriate to diagnosis, as well as by direct sequencing for IDH1/2 and P53. No unusual genetic features were detected in our cohort; further, the 4 GBMs we did identify did not have clinical features of secondary glioblastomas nor did any of the four manifest IDH-1 immunohistochemical expression or IDH1/2 mutations, as might be expected in secondary GBMs. Conversely, PTEN loss and EGFR expression, features often found in primary GBMs, but seldom identified in secondary GBMs, were found in 3 of 4 GBMs. We conclude that gliomas in MS patients have genetic features paralleling counterparts in non-MS patients. There is no strong genetic evidence for GBMs to be secondary GBMs.

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Acknowledgments

The authors gratefully acknowledge the expert manuscript preparation of Mrs. Diane Hutchinson, the photographic expertise of Ms. Lisa Litzenberger, and the assistance of Dr. Wilbur Franklin, director of the CMOCO molecular diagnostics laboratory facility at University of Colorado, for performing IDH-1/2 and P53 gene sequence testing.

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Authors and Affiliations

  1. University of Colorado at Denver, Anschutz Medical Campus, 12631 East 17th Avenue, Aurora, CO, 80045, USA

    Adam Khalil

  2. Departments of Pathology, University of Colorado at Denver, Anschutz Medical Campus, 12631 East 17th Avenue, Aurora, CO, 80045, USA

    Hilary Serracino & B. K. Kleinschmidt-DeMasters

  3. Departments of Neurology, University of Colorado at Denver, Anschutz Medical Campus, 12631 East 17th Avenue, Aurora, CO, 80045, USA

    Denise M. Damek, Douglas Ney & B. K. Kleinschmidt-DeMasters

  4. Departments of Neurosurgery, University of Colorado at Denver, Anschutz Medical Campus, 12631 East 17th Avenue, Aurora, CO, 80045, USA

    Denise M. Damek, Douglas Ney, Kevin O. Lillehei & B. K. Kleinschmidt-DeMasters

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  1. Adam Khalil
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  2. Hilary Serracino
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  3. Denise M. Damek
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  6. B. K. Kleinschmidt-DeMasters
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Correspondence to B. K. Kleinschmidt-DeMasters.

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Khalil, A., Serracino, H., Damek, D.M. et al. Genetic characterization of gliomas arising in patients with multiple sclerosis. J Neurooncol 109, 261–272 (2012). https://doi.org/10.1007/s11060-012-0888-2

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  • DOI: https://doi.org/10.1007/s11060-012-0888-2

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