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

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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.

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Acknowledgments

This work was supported by grants from FAPESP (The State of São Paulo Research Foundation: 2011/19629-0; 2011/16221-0) and GRAACC (Grupo de Apoio ao Adolescente e Criança com Câncer).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Standards

Samples from each Astrocytoma tumor were collected after informed consent was signed by patients/guardians according to the university’s institutional review board (IRB/Federal University of São Paulo no 0475/11).

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Authors and Affiliations

  1. 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

    Gabriela Rampazzo Cruz, Indhira Dias Oliveira, Mário Del Giudice Paniago, Maria Teresa de Seixas Alves, Andrea Maria Capellano, Nasjla Saba-Silva, Sérgio Cavalheiro & Silvia Regina Caminada Toledo

  2. Division of Genetics, Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, SP, Brazil

    Gabriela Rampazzo Cruz, Indhira Dias Oliveira, Laís Moraes, Janete Maria Cerutti & Silvia Regina Caminada Toledo

  3. Department of Pathology, Federal University of São Paulo, São Paulo, SP, Brazil

    Maria Teresa de Seixas Alves

  4. Departament of Neurology, Federal University of São Paulo, São Paulo, SP, Brazil

    Sérgio Cavalheiro

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  1. Gabriela Rampazzo Cruz
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  2. Indhira Dias Oliveira
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Correspondence to Silvia Regina Caminada Toledo.

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Cruz, G.R., Dias Oliveira, I., Moraes, L. et al. Analysis of KIAA1549–BRAF fusion gene expression and IDH1/IDH2 mutations in low grade pediatric astrocytomas. J Neurooncol 117, 235–242 (2014). https://doi.org/10.1007/s11060-014-1398-1

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  • DOI: https://doi.org/10.1007/s11060-014-1398-1

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