title: Analysis of KIAA1549-BRAF fusion gene expression and IDH1/IDH2 mutations in low grade pediatric astrocytomas.
abstract: Low-grade astrocytomas comprise about 30 % of the central nervous system tumors in children. Several investigations have searched a correlation between the BRAF gene fusions alterations and mutations at IDH1 and IDH2 genes in low grade pediatric astrocytomas. This study identified the expression of KIAA1549-BRAF fusion gene and BRAF V600E mutation, mutations at exon 4 of the IDH1 and IDH2 genes in samples of pilocytic astrocytomas (PA) and grade-II astrocytomas (A-II) pediatric patients. The correlation between these alterations and the clinical profile of the patients was also evaluated. Eighty-two samples of low-grade astrocytomas (65 PA and 17 A-II) were analyzed by PCR and sequencing for each of the targets identified. We identified the KIAA1549-BRAF fusion transcript in 45 % of the samples. BRAF V600E and BRAFins598T mutations were detected in 7 and 1 % of the samples, respectively. Mutations in the R132/R172 residues of the IDH1/IDH2 genes were detected in only two samples, and the G105G polymorphism (rs11554137:C>T) was identified in ten patients. Additionally, we observed two mutations out of the usual hotspots at IDH1 and IDH2 genes. We observed a smaller frequency of mutations in IDHs genes than previously described, but since the prior studies were composed of adult or mixed (adults and children) samples, we believe that our results represent a relevant contribution to the growing knowledge in low grade childhood astrocytomas.
authors: Department of Pediatrics, Pediatrics Oncology Institute-GRAACC (Grupo de Apoio ao Adolescente e à Criança com Câncer), UNIFESP (Federal University of São Paulo), Rua Botucatu, no 743, Floor 8 - Genetics Laboratory, Vila Clementino, São Paulo, SP, 04023-062, Brazil, gabi.rampazzo@gmail.com.
authors: Gabriela Rampazzo
authors: GR
authors: Cruz
authors: Indhira
authors: I
authors: Dias Oliveira
authors: Laís
authors: L
authors: Moraes
authors: Mário
authors: M
authors: Del Giudice Paniago
authors: Maria Teresa
authors: MT
authors: de Seixas Alves
authors: Andrea Maria
authors: AM
authors: Capellano
authors: Nasjla
authors: N
authors: Saba-Silva
authors: Sérgio
authors: S
authors: Cavalheiro
authors: Janete Maria
authors: JM
authors: Cerutti
authors: Silvia Regina Caminada
authors: SR
authors: Toledo
mesh_terms: D000293:Adolescent; D001254:Astrocytoma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D009154:Mutation; D060787:Neoplasm Grading; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D015514:Oncogene Proteins, Fusion; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf