title: BRAF V600E mutations are common in pleomorphic xanthoastrocytoma: diagnostic and therapeutic implications.
abstract: Pleomorphic xanthoastrocytoma (PXA) is low-grade glial neoplasm principally affecting children and young adults. Approximately 40% of PXA are reported to recur within 10 years of primary resection. Upon recurrence, patients receive radiation therapy and conventional chemotherapeutics designed for high-grade gliomas. Genetic changes that can be targeted by selective therapeutics have not been extensively evaluated in PXA and ancillary diagnostic tests to help discriminate PXA from other pleomorphic and often more aggressive astrocytic malignancies are limited. In this study, we apply the SNaPshot multiplexed targeted sequencing platform in the analysis of brain tumors to interrogate 60 genetic loci that are frequently mutated in 15 cancer genes. In our analysis we detect BRAF V600E mutations in 12 of 20 (60%) WHO grade II PXA, in 1 of 6 (17%) PXA with anaplasia and in 1 glioblastoma arising in a PXA. Phospho-ERK was detected in all tumors independent of the BRAF mutation status. BRAF duplication was not detected in any of the PXA cases. BRAF V600E mutations were identified in only 2 of 71 (2.8%) glioblastoma (GBM) analyzed, including 1 of 9 (11.1%) giant cell GBM (gcGBM). The finding that BRAF V600E mutations are common in the majority of PXA has important therapeutic implications and may help in differentiating less aggressive PXAs from lethal gcGBMs and GBMs.
authors.affiliation: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America. ssantagata@partners.org
authors.forename: Dora
authors.initials: D
authors.lastname: Dias-Santagata
authors.forename: Quynh
authors.initials: Q
authors.lastname: Lam
authors.forename: Kathy
authors.initials: K
authors.lastname: Vernovsky
authors.forename: Natalie
authors.initials: N
authors.lastname: Vena
authors.forename: Jochen K
authors.initials: JK
authors.lastname: Lennerz
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Borger
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Batchelor
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.forename: A John
authors.initials: AJ
authors.lastname: Iafrate
authors.forename: Azra H
authors.initials: AH
authors.lastname: Ligon
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
authors.forename: Sandro
authors.initials: S
authors.lastname: Santagata
mesh_terms: D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005838:Genotype; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases