{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:12:46Z","timestamp":1789693966617,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,12,23]],"date-time":"2013-12-23T00:00:00Z","timestamp":1387756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Brainstem gangliogliomas (<jats:styled-content style=\"fixed-case\">GGs<\/jats:styled-content>), 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 <jats:styled-content style=\"fixed-case\"><jats:italic>BRAF<\/jats:italic><\/jats:styled-content><jats:italic> c.1799<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>T<\/jats:italic><\/jats:styled-content>&gt;<jats:styled-content style=\"fixed-case\"><jats:italic>A<\/jats:italic><\/jats:styled-content> (p.<jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>600<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>) (<jats:styled-content style=\"fixed-case\"><jats:italic>BRAF<jats:sup>V600E<\/jats:sup><\/jats:italic><\/jats:styled-content>) mutations are harbored in roughly 50% of collective <jats:styled-content style=\"fixed-case\">GGs<\/jats:styled-content> taken from all anatomical sites. Large numbers of pediatric brainstem <jats:styled-content style=\"fixed-case\">GGs<\/jats:styled-content>, however, have not been specifically assessed and anatomic\u2014and age\u2010restricted assessment of genetic and biological factors are becoming increasingly important. Pediatric brainstem <jats:styled-content style=\"fixed-case\">GGs<\/jats:styled-content> (n\u2009=\u200913), non\u2010brainstem <jats:styled-content style=\"fixed-case\">GGs<\/jats:styled-content> (n\u2009=\u200911) and brainstem pilocytic astrocytomas (<jats:styled-content style=\"fixed-case\">PAs<\/jats:styled-content>) (n\u2009=\u20098) were screened by standard Sanger <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sequencing of <jats:styled-content style=\"fixed-case\"><jats:italic>BRAF<\/jats:italic><\/jats:styled-content> exon 15. Five of 13 (38%) pediatric <jats:styled-content style=\"fixed-case\">GG<\/jats:styled-content> harbored a definitive <jats:styled-content style=\"fixed-case\"><jats:italic>BRAF<jats:sup>V600E<\/jats:sup><\/jats:italic><\/jats:styled-content> mutation, with two others exhibiting an equivocal result by this method. <jats:styled-content style=\"fixed-case\"><jats:italic>BRAF<jats:sup>V600E<\/jats:sup><\/jats:italic><\/jats:styled-content> was also seen in five of 11 (45%) non\u2010brainstem <jats:styled-content style=\"fixed-case\">GGs<\/jats:styled-content> and one of eight (13%) brainstem <jats:styled-content style=\"fixed-case\">PAs<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>1 immunostaining for <jats:styled-content style=\"fixed-case\"><jats:italic>BRAF<jats:sup>V600E<\/jats:sup><\/jats:italic><\/jats:styled-content> showed concordance with sequencing in nine of nine brainstem <jats:styled-content style=\"fixed-case\">GGs<\/jats:styled-content> including the two cases equivocal by <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>anger. The equivocal brainstem <jats:styled-content style=\"fixed-case\">GGs<\/jats:styled-content> were subsequently shown to harbor <jats:styled-content style=\"fixed-case\"><jats:italic>BRAF<jats:sup>V600E<\/jats:sup><\/jats:italic><\/jats:styled-content> using a novel, more sensitive, <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010sequencing approach, yielding a final <jats:styled-content style=\"fixed-case\"><jats:italic>BRAF<jats:sup>V600E<\/jats:sup><\/jats:italic><\/jats:styled-content> mutation frequency of 54% (seven of 13) in brainstem <jats:styled-content style=\"fixed-case\">GGs<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\"><jats:italic>BRAF<jats:sup>V600E<\/jats:sup><\/jats:italic><\/jats:styled-content>\u2010targeted therapeutics should be a consideration for the high percentage of pediatric brainstem <jats:styled-content style=\"fixed-case\">GGs<\/jats:styled-content> refractory to conventional therapies.<\/jats:p>","DOI":"10.1111\/bpa.12103","type":"journal-article","created":{"date-parts":[[2013,11,19]],"date-time":"2013-11-19T00:53:12Z","timestamp":1384822392000},"page":"173-183","source":"Crossref","is-referenced-by-count":59,"title":["Pediatric Brainstem Gangliogliomas Show <scp><i>BRAF<sup>V600E<\/sup><\/i><\/scp> Mutation in a High Percentage of Cases"],"prefix":"10.1111","volume":"24","author":[{"given":"Andrew M.","family":"Donson","sequence":"first","affiliation":[{"name":"Department of Pediatrics Children's Hospital Colorado  Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bette K.","family":"Kleinschmidt\u2010DeMasters","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Hospital Colorado  Aurora CO"},{"name":"Department of Neurosurgery Children's Hospital Colorado  Aurora CO"},{"name":"Department of Surgical Pathology University of Colorado Denver  Aurora CO"},{"name":"Department of Neurology University of Colorado Denver  Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dara L.","family":"Aisner","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology University of Colorado Denver  Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne T.","family":"Bemis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Minnesota Medical School\u2010Duluth  Duluth MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane K.","family":"Birks","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Children's Hospital Colorado  Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean M. 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