title: Combined molecular analysis of BRAF and IDH1 distinguishes pilocytic astrocytoma from diffuse astrocytoma.
abstract: Separation of pilocytic astrocytoma from diffuse astrocytomas frequently poses problems mostly related to small sample size. Precise classification and grading are essential due to different therapeutic strategies prompted by diagnoses of pilocytic astrocytoma WHO grade I, diffuse astrocytomas WHO grade II or anaplastic astrocytoma WHO grade III. Recently, genomic aberrations with a high specificity for distinct glioma entities have been described. Pilocytic astrocytomas carry a duplication at chromosome band 7q34 containing a BRAF-KIAA1549 gene fusion in the majority of cases. IDH1 mutations are observed very frequently in adult astrocytomas and IDH2 mutations have been reported in some astrocytomas. We examined a series of 120 astrocytomas including 70 pilocytic astrocytomas WHO grade I and 50 diffuse astrocytomas WHO grade II for both, BRAF-KIAA1549 fusion with a newly developed FISH assay and mutations in IDH1 and IDH2 by direct sequencing. Pilocytic astrocytomas contained the BRAF fusion in 49 cases (70%) but neither IDH1 nor IDH2 mutations. Astrocytomas WHO grade II exhibited IDH1 mutations in 38 cases (76%) but neither IDH2 mutations nor BRAF fusions. Thus, combined molecular analysis of BRAF and IDH1 is a sensitive and highly specific approach to separate pilocytic astrocytoma from diffuse astrocytoma.
authors: Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universität Heidelberg, 69120 Heidelberg, Germany.
authors: Andrey
authors: A
authors: Korshunov
authors: Jochen
authors: J
authors: Meyer
authors: David
authors: D
authors: Capper
authors: Arne
authors: A
authors: Christians
authors: Marc
authors: M
authors: Remke
authors: Hendrik
authors: H
authors: Witt
authors: Stefan
authors: S
authors: Pfister
authors: Andreas
authors: A
authors: von Deimling
authors: Christian
authors: C
authors: Hartmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000175:diagnosis* / Q000235:genetics; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+); C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf