title: A novel, potentially targetable TMEM106B-BRAF fusion in pleomorphic xanthoastrocytoma.
abstract: Pleomorphic xanthoastrocytoma (PXA) is a World Health Organization (WHO) Grade II glioma occurring primarily in children and young adults. Most PXAs harbor the known activating mutationBRAFV600E. We report a case of locally recurrent PXA with anaplastic features in a 10-yr-old female. The PXA was negative by immunohistochemical (IHC) staining forBRAFV600E mutation. Whole-exome and transcriptome sequencing of the tumor confirmed the absence ofBRAFV600E, but identified copy-number alterations (including loss of the tumor suppressorCDKN2A) and a novelTMEM106B-BRAFfusion. Based on similar BRAF fusion proteins, this novel fusion is predicted to result in activation of BRAF signaling. Demonstration of positive IHC for phospho-ERK1/2 and phospho-MEK1/2 supported this prediction, and implicated MEK inhibitors as a potential therapeutic strategy.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Hsiao
authors.affiliation: Department of Pediatrics, NYU Langone Medical Center, New York, New York 10016, USA.
authors.forename: Matthias A
authors.initials: MA
authors.lastname: Karajannis
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Diolaiti
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Mahesh M
authors.initials: MM
authors.lastname: Mansukhani
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Julia Glade
authors.initials: JG
authors.lastname: Bender
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Kung
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Garvin
mesh_terms: D001254:Astrocytoma / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics; D002648:Child; D005260:Female; D005910:Glioma / Q000235:genetics; D006801:Humans; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D000073359:Exome Sequencing
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: neoplasm of the central nervous system