title: Analysis of IDH1-R132 mutation, BRAF V600 mutation and KIAA1549-BRAF fusion transcript status in central nervous system tumors supports pediatric tumor classification.
abstract: OBJECTIVE
  Gliomas are the leading cause of cancer-related morbidity in children and comprise a clinical, histological and molecular heterogenous group of CNS tumors. Appropriate treatment of these tumors relies on correct classification into tumor types and malignancy grades.
  
  
  METHODS
  We examined 170 (0-18 years) pediatric and 131 (19-35 years) young adult brain tumors including pilocytic astrocytomas (PAs), pilomyxoid astrocytomas (PMAs), diffuse astrocytomas (DAs), gangliogliomas, dysembryoplastic neuroepithelial tumors (DNTs) and pleomorphic xanthoastrocytomas (PXAs) for IDH1 and BRAF mutation/BRAF fusion gene status. The obtained data were compared to results in 464 (<35 years) adult brain tumors. In 32 tumors with an oligodendroglial or mixed glioma differentiation, additionally the LOH1p/19q status was determined.
  
  
  RESULTS
  By combining immunohistochemistry and molecular methods, IDH1/2 mutations were observed in 6 pediatric, 35 young adult and 43 adult tumors of the astrocytic/oligodendroglial lineage. BRAF V600E mutations (20 pediatric, 7 young adults and 2 adults) were found mostly in gangliogliomas, PXAs, few astrocytomas and few DNTs. Except for one DA case, BRAF fusions (35 pediatric, 8 young adults and 2 adults) were restricted to PA and PMA and associated with age and infratentorial location. All mutations were mutually exclusive and always present in the primary tumor. Two-thirds of all pediatric samples harbored one of the three examined mutations.
  
  
  CONCLUSIONS
  Combination of IDH1-R132, BRAF V600 and KIAA1549-BRAF fusion analysis is therefore a useful tool to increase diagnostic accuracy in pediatric gliomas.
authors.affiliation: Department of Neuropathology, Institute of Pathology and Neuropathology, University of Tübingen, Calwerstr. 3, 72076, Tübingen, Germany.
authors.forename: Midea
authors.initials: M
authors.lastname: Gierke
authors.affiliation: Department of Pathology, University of Tübingen, Tübingen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Sperveslage
authors.affiliation: Department of Neuropathology, Institute of Pathology and Neuropathology, University of Tübingen, Calwerstr. 3, 72076, Tübingen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Schwab
authors.affiliation: Department of Neuropathology, Institute of Pathology and Neuropathology, University of Tübingen, Calwerstr. 3, 72076, Tübingen, Germany.
authors.forename: Rudi
authors.initials: R
authors.lastname: Beschorner
authors.affiliation: Pediatric Oncology, University Childrens Hospital, University of Tübingen, Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Ebinger
authors.affiliation: Department of Neurosurgery, University of Tuebingen, Tübingen, Germany.
authors.forename: Martin U
authors.initials: MU
authors.lastname: Schuhmann
authors.affiliation: Department of Neuropathology, Institute of Pathology and Neuropathology, University of Tübingen, Calwerstr. 3, 72076, Tübingen, Germany. jens.schittenhelm@med.uni-tuebingen.de.
authors.forename: Jens
authors.initials: J
authors.lastname: Schittenhelm
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D007231:Infant, Newborn; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: C568616:BRAF-KIAA1549 fusion protein, human; D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF V600E; Classification; Glioma; IDH1; KIAA1549–BRAF