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Analysis of IDH1-R132 mutation, BRAF V600 mutation and KIAA1549–BRAF fusion transcript status in central nervous system tumors supports pediatric tumor classification

  • Original Article – Cancer Research
  • Published:
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Abstract

Objective

Gliomas are the leading cause of cancer-related morbidity in children and comprise a clinical, histological and molecular heterogenous group of CNS tumors. Appropriate treatment of these tumors relies on correct classification into tumor types and malignancy grades.

Methods

We examined 170 (0–18 years) pediatric and 131 (19–35 years) young adult brain tumors including pilocytic astrocytomas (PAs), pilomyxoid astrocytomas (PMAs), diffuse astrocytomas (DAs), gangliogliomas, dysembryoplastic neuroepithelial tumors (DNTs) and pleomorphic xanthoastrocytomas (PXAs) for IDH1 and BRAF mutation/BRAF fusion gene status. The obtained data were compared to results in 464 (<35 years) adult brain tumors. In 32 tumors with an oligodendroglial or mixed glioma differentiation, additionally the LOH1p/19q status was determined.

Results

By combining immunohistochemistry and molecular methods, IDH1/2 mutations were observed in 6 pediatric, 35 young adult and 43 adult tumors of the astrocytic/oligodendroglial lineage. BRAF V600E mutations (20 pediatric, 7 young adults and 2 adults) were found mostly in gangliogliomas, PXAs, few astrocytomas and few DNTs. Except for one DA case, BRAF fusions (35 pediatric, 8 young adults and 2 adults) were restricted to PA and PMA and associated with age and infratentorial location. All mutations were mutually exclusive and always present in the primary tumor. Two-thirds of all pediatric samples harbored one of the three examined mutations.

Conclusion

Combination of IDH1-R132, BRAF V600 and KIAA1549–BRAF fusion analysis is therefore a useful tool to increase diagnostic accuracy in pediatric gliomas.

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Acknowledgments

This work was supported by the Ludwig-Hiermaier foundation of applied cancer research (Grant D30.15610).

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Authors and Affiliations

  1. Department of Neuropathology, Institute of Pathology and Neuropathology, University of Tübingen, Calwerstr. 3, 72076, Tübingen, Germany

    Midea Gierke, David Schwab, Rudi Beschorner & Jens Schittenhelm

  2. Department of Pathology, University of Tübingen, Tübingen, Germany

    Jan Sperveslage

  3. Pediatric Oncology, University Childrens Hospital, University of Tübingen, Tübingen, Germany

    Martin Ebinger

  4. Department of Neurosurgery, University of Tuebingen, Tübingen, Germany

    Martin U. Schuhmann

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  1. Midea Gierke
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  2. Jan Sperveslage
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  4. Rudi Beschorner
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  5. Martin Ebinger
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  6. Martin U. Schuhmann
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Correspondence to Jens Schittenhelm.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Utilization of human samples was in accordance with the university ethics commission (Approval Numbers: 576/2011BO2, 040/2012BO2).

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Gierke, M., Sperveslage, J., Schwab, D. et al. Analysis of IDH1-R132 mutation, BRAF V600 mutation and KIAA1549–BRAF fusion transcript status in central nervous system tumors supports pediatric tumor classification. J Cancer Res Clin Oncol 142, 89–100 (2016). https://doi.org/10.1007/s00432-015-2006-2

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