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Association of molecular alterations, including BRAF, with biology and outcome in pilocytic astrocytomas

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Abstract

Pilocytic astrocytoma (PA) is the most common glioma in the pediatric population. PAs can exhibit variable behavior that does not always correlate with location. Although oncogenic rearrangements of the BRAF gene have recently been described in PAs, it is not clear whether such alterations have an impact on outcome. An institutional cohort of 147 PAs (118 with outcome data) from both cerebellar and non-cerebellar locations (spine, diencephalon, midbrain, brainstem, and cortex) was utilized in this study. Parameters included quantification of characteristic morphologic variables as well as genes and molecular loci previously shown to be of relevance in high-grade gliomas, including 1p, 9p, 10q, 17p, 19q, and BRAF. Neither 1p, 9p, and 10q nor 19q showed significant association with outcome in PAs, although p16 deletion was more common in PAs of the midbrain, brainstem, and spinal cord. Loss of heterozygosity on 17p13 correlated with increased risk of recurrence in cerebellar tumors. BRAF gene rearrangements were more common in cerebellar tumors than non-cerebellar tumors and associated with classic biphasic histology in the cerebellum. However, clinical outcome was independent of BRAF status. The molecular biology of PAs differs according to location, yet BRAF rearrangements do not appear to produce PAs with different behavior. Nevertheless, such tumors may have altered sensitivity to pathway-specific adjuvant therapy. Additionally, deletion on 17p13 may be an adverse prognostic biomarker in cerebellar tumors.

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Acknowledgments

The authors thank Colleen Lovell and Judy Burnham for their histological expertise; Kathy Cieply, John Salvatore, and Carol Sherer for their assistance in fluorescence in situ hybridization; and Marianne Notaro and Michelle Bisceglia for TMA preparation. This study was funded by a Brain Tumor Society Award from the Pediatric Low Grade Glioma Foundation and NIH R01 NS37704. CH was supported by a Callie Rohr/American Brain Tumor Association Fellowship. Portions of this data were presented at the American Association of Neuropathologists 2009 Annual Meeting in San Antonio, TX.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, University of Kentucky, 800 Rose St., Lexington, KY, 40536, USA

    Craig Horbinski

  2. Department of Pathology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA, 15213, USA

    Ronald L. Hamilton & Yuri Nikiforov

  3. Department of Pediatric Neurosurgery, Children’s Hospital of Pittsburgh, 45th Street and Penn Avenue, Pittsburgh, PA, 15201, USA

    Ian F. Pollack

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  1. Craig Horbinski
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Correspondence to Craig Horbinski.

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Horbinski, C., Hamilton, R.L., Nikiforov, Y. et al. Association of molecular alterations, including BRAF, with biology and outcome in pilocytic astrocytomas. Acta Neuropathol 119, 641–649 (2010). https://doi.org/10.1007/s00401-009-0634-9

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  • DOI: https://doi.org/10.1007/s00401-009-0634-9

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