title: Molecular characterization of disseminated pilocytic astrocytomas.
abstract: OBJECTIVE
  Pilocytic astrocytomas represent the most common paediatric tumours of the central nervous system. Dissemination through the ventricular system occurs rarely in patients with pilocytic astrocytomas; however, it is more common in infants with diencephalic tumours, and is associated with a poor outcome. Despite histological similarities with classic pilocytic astrocytomas, it is still unclear whether disseminated pilocytic astrocytomas may have specific molecular features.
  
  
  METHODS
  Seventeen disseminated pilocytic astrocytomas were investigated using the molecular inversion probe array and screened for the presence of gene fusions (KIAA1549-BRAF) and mutations (BRAF, RAS and FGFR1).
  
  
  RESULTS
  Along with evidence of a constitutive MAPK activation in all cases, the molecular inversion probe array, fluorescence in situ hybridization analysis and mutational study revealed KIAA1549-BRAF fusions in 66% and BRAF(V600E) mutations in 5% of cases. No KRAS, HRAS, NRAS or FGFR1 mutations were found.
  
  
  CONCLUSIONS
  disseminated pilocytic astrocytomas showed genetic features similar to classic pilocytic astrocytoma, including a similar incidence of KIAA1549-BRAF fusions, BRAF mutations and a stable genetic profile. Given common activation of the MAPK pathway, the use of specific inhibitors can be hypothesized for the treatment of disseminated pilocytic astrocytomas, along with standard chemo- and/or radiotherapy.
authors.affiliation: Institute of Neuropathology, University of Bonn, Bonn, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gessi
authors.affiliation: Institute of Neuropathology, University of Bonn, Bonn, Germany.
authors.forename: A C
authors.initials: AC
authors.lastname: Engels
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Lambert
authors.affiliation: Department of Forensic Medicine, University of Hannover Medical School, Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Rothämel
authors.affiliation: Department of Pediatric Oncology, Klinikum Augsburg, Augsburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: von Hornstein
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: V P
authors.initials: VP
authors.lastname: Collins
authors.affiliation: Institute of Neuropathology, University of Bonn, Bonn, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Denkhaus
authors.affiliation: Department of Pediatric Oncology, Klinikum Augsburg, Augsburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Gnekow
authors.affiliation: Institute of Neuropathology, University of Bonn, Bonn, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Pietsch
mesh_terms: D000293:Adolescent; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics
chemical_list: C568616:BRAF-KIAA1549 fusion protein, human; D015514:Oncogene Proteins, Fusion; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; ERK; KIAA1549-BRAF fusion; MAPK pathway; disseminated pilocytic astrocytoma; low grade gliomas