Cruz Gabriela Rampazzo, Dias Oliveira Indhira, Moraes Laís, Del Giudice Paniago Mário, de Seixas Alves Maria Teresa, Capellano Andrea Maria, Saba-Silva Nasjla, Cavalheiro Sérgio, Cerutti Janete Maria, Toledo Silvia Regina Caminada
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,
J Neurooncol. 2014 Apr;117(2):235-42. doi: 10.1007/s11060-014-1398-1. Epub 2014 Feb 17.
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.
低级别星形细胞瘤约占儿童中枢神经系统肿瘤的30%。多项研究探寻了低级别儿童星形细胞瘤中BRAF基因融合改变与IDH1和IDH2基因的突变之间的相关性。本研究确定了儿童毛细胞型星形细胞瘤（PA）和II级星形细胞瘤（A-II）患者样本中KIAA1549-BRAF融合基因的表达、BRAF V600E突变、IDH1和IDH2基因第4外显子的突变情况。还评估了这些改变与患者临床特征之间的相关性。对82例低级别星形细胞瘤样本（65例PA和17例A-II）进行了PCR和测序，以分析每个确定的靶点。我们在45%的样本中鉴定出了KIAA1549-BRAF融合转录本。分别在7%和1%的样本中检测到BRAF V600E和BRAFins598T突变。仅在两个样本中检测到IDH1/IDH2基因R132/R172位点的突变，在10例患者中鉴定出G105G多态性（rs11554137:C>T）。此外，我们在IDH1和IDH2基因中观察到两个非常见热点区域的突变。我们观察到IDH基因的突变频率低于先前报道，但由于先前的研究由成人或混合样本（成人和儿童）组成，我们认为我们的结果为低级别儿童星形细胞瘤不断增长的知识体系做出了相关贡献。
