Analysis of KIAA1549-BRAF fusion gene expression and IDH1/IDH2 mutations in low grade pediatric astrocytomas

Author(s)

Cruz, Gabriela Rampazzo ^{[1, 2]} ; Oliveira, Indhira Dias ^{[1, 2]} ; Moraes, Lais ^[1] ; Paniago, Mario Del Giudice ^[2] ; de Seixas Alves, Maria Teresa ^{[3, 2]} ; Capellano, Andrea Maria ^[2] ; Saba-Silva, Nasjla ^[2] ; Cavalheiro, Sergio ^{[4, 2]} ; Cerutti, Janete Maria ^[1] ; Caminada Toledo, Silvia Regina ^{[1, 2]}

Affiliation

^[1] Univ Fed Sao Paulo, Dept Morphol & Genet, Div Genet, Sao Paulo - Brazil

^[2] UNIFESP Fed Univ Sao Paulo, Dept Pediat, Pediat Oncol Inst, GRAACC Grp Apoio Adolescente & Crianca Canc, Genet, BR-04023062 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Pathol, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Dept Neurol, Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF NEURO-ONCOLOGY; v. 117, n. 2, p. 235-242, APR 2014.
• Web of Science Citations: 19

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. (AU)

• FAPESP's process: 11/19629-0 - Prognostic markers investigation in brain tumors most frequenttly in childhood and adolescents: pilocytic astrocytoma and medulloblastoma
• Grantee: Silvia Regina Caminada de Toledo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/16221-0 - Analysis of gene expression profile in medulloblastoma development and its relationship to patients clinical outcome
• Grantee: Bruna Mascaro Cordeiro de Azevedo
• Support Opportunities: Scholarships in Brazil - Master