Open AccessPediatric Brainstem Gangliogliomas Show BRAF V600E Mutation in a High Percentage of Cases
Author(s) -
Donson Andrew M.,
KleinschmidtDeMasters Bette K.,
Aisner Dara L.,
Bemis Lynne T.,
Birks Diane K.,
Levy Jean M. Mulcahy,
Smith Amy A.,
Handler Michael H.,
Foreman Nicholas K.,
Rush Sarah Z.
Publication year - 2014
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12103
Subject(s) - brainstem , medicine , sanger sequencing , exon , concordance , mutation , cancer research , biology , genetics , gene
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.1799 T > A (p. V 600 E ) ( BRAF V600E ) 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 BRAF V600E mutation, with two others exhibiting an equivocal result by this method. BRAF V600E was also seen in five of 11 (45%) non‐brainstem GGs and one of eight (13%) brainstem PAs . VE 1 immunostaining for BRAF V600E showed concordance with sequencing in nine of nine brainstem GGs including the two cases equivocal by S anger. The equivocal brainstem GGs were subsequently shown to harbor BRAF V600E using a novel, more sensitive, RNA ‐sequencing approach, yielding a final BRAF V600E mutation frequency of 54% (seven of 13) in brainstem GGs . BRAF V600E ‐targeted therapeutics should be a consideration for the high percentage of pediatric brainstem GGs refractory to conventional therapies.