A novel GIT2-BRAF fusion in pilocytic astrocytoma

Jeffrey Helgager,Hart G Lidov,Keith L Ligon,Navin R Mahadevan,Mark W Kieran,Sanda Alexandrescu

doi:10.1186/s13000-017-0669-5

Abstract

BackgroundKIAA1549-BRAF fusion is the most common genetic event in pilocytic astrocytoma (PA), and leads to activation of the mitogen activated protein kinase (MAPK) signaling pathway. Fusions of BRAF with other partner genes, as well as other genetic alterations not involving BRAF but also leading to MAPK pathway activation have been described rarely.Case presentationWe present a new fusion partner in the low-grade glioma of a 10-year-old male, who presented with headaches and recent episodes of seizures. Magnetic resonance imaging (MRI) demonstrated a right temporal lobe tumor. Histological and immunohistochemical evaluation, and a next generation sequencing assay (Oncopanel, Illumina, 500 genes) including breaKmer analysis for chromosomal rearrangements were performed.Histology was remarkable for a low-grade glioma composed of mildly atypical astrocytes with piloid processes, in a focally microcystic background. Mitoses were not seen; unequivocal Rosenthal fibers or eosinophilic granular bodies were absent. The tumor was positive for OLIG2 and GFAP and negative for BRAF V600E and IDH1 R132H mutant protein immunostains. Oncopanel showed low SOX2 (3q26.33) copy number gain, and no gains at 7q34. There were no significant single nucleotide variants. BreaKmer detected a GIT2-BRAF fusion with loss of BRAF exons 1–8. The integrated diagnosis was low-grade glioma with piloid features, most consistent with pilocytic astrocytoma, WHO grade I.ConclusionGIT2-BRAF fusion has not been reported in the literature in any tumor. Given that the BRAF sequence deleted is identical to that seen in other fusion events in PA, it most likely acts as tumor driver by activation of the MAPK pathway.

Highlights

KIAA1549-BRAF fusion is the most common genetic event in pilocytic astrocytoma (PA), and leads to activation of the mitogen activated protein kinase (MAPK) signaling pathway
Given that the BRAF sequence deleted is identical to that seen in other fusion events in PA, it most likely acts as tumor driver by activation of the MAPK pathway
The tumor demonstrated extensive immunostaining with GFAP (Fig. 2e) and OLIG2, and was negative for BRAF V600E and for IDH1 R132H mutant protein

Summary

Introduction

KIAA1549-BRAF fusion is the most common genetic event in pilocytic astrocytoma (PA), and leads to activation of the mitogen activated protein kinase (MAPK) signaling pathway. Histology was remarkable for a low-grade glioma composed of mildly atypical astrocytes with piloid processes, in a focally microcystic background. Surgical excision alone is frequently curative, with a survival rate of greater than 95% at 10-year follow-up [2, 6] This benign clinical course underscores the importance of accurately distinguishing these tumors from other glial neoplasms. The histological diagnosis can be problematic because PAs can demonstrate mitoses, foci of increased proliferative labeling index by immunohistochemistry for MIB1, microvascular proliferation and sometimes geographic necrosis, all features that are encountered in high-grade gliomas [5].

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Discussion

Conclusion