Pediatric brainstem gangliogliomas show BRAFV600E mutation in a high percentage of cases

Andrew M. Donson, Bette K. Kleinschmidt-Demasters, Dara L. Aisner, Lynne T. Bemis, Diane K. Birks, Jean M.Mulcahy Levy, Amy A. Smith, Michael H. Handler, Nicholas K. Foreman, Sarah Z. Rush

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Brainstem gangliogliomas (GGs), often cannot be resected, have a much poorer prognosis than those located in more common supratentorial sites and may benefit from novel therapeutic approaches. Therapeutically targetable BRAF c.1799T>A (p.V600E) (BRAFV600E) mutations are harbored in roughly 50% of collective GGs taken from all anatomical sites. Large numbers of pediatric brainstem GGs, however, have not been specifically assessed and anatomic - and age-restricted assessment of genetic and biological factors are becoming increasingly important. Pediatric brainstem GGs (n = 13), non-brainstem GGs (n = 11) and brainstem pilocytic astrocytomas (PAs) (n = 8) were screened by standard Sanger DNA sequencing of BRAF exon 15. Five of 13 (38%) pediatric GG harbored a definitive BRAFV600E mutation, with two others exhibiting an equivocal result by this method. BRAFV600E was also seen in five of 11 (45%) non-brainstem GGs and one of eight (13%) brainstem PAs. VE1 immunostaining for BRAFV600E showed concordance with sequencing in nine of nine brainstem GGs including the two cases equivocal by Sanger. The equivocal brainstem GGs were subsequently shown to harbor BRAFV600E using a novel, more sensitive, RNA-sequencing approach, yielding a final BRAFV600E mutation frequency of 54% (seven of 13) in brainstem GGs. BRAFV600E-targeted therapeutics should be a consideration for the high percentage of pediatric brainstem GGs refractory to conventional therapies.

Original languageEnglish (US)
Pages (from-to)173-183
Number of pages11
JournalBrain Pathology
Volume24
Issue number2
DOIs
StatePublished - Mar 1 2014

    Fingerprint

Keywords

  • BRAF
  • brainstem
  • brainstem pilocytic astrocytomas
  • ganglioglioma
  • pediatric

Cite this

Donson, A. M., Kleinschmidt-Demasters, B. K., Aisner, D. L., Bemis, L. T., Birks, D. K., Levy, J. M. M., Smith, A. A., Handler, M. H., Foreman, N. K., & Rush, S. Z. (2014). Pediatric brainstem gangliogliomas show BRAFV600E mutation in a high percentage of cases. Brain Pathology, 24(2), 173-183. https://doi.org/10.1111/bpa.12103