KIAA1549:BRAF FUSION GENE IN PEDIATRIC BRAIN TUMORS OF DIFFERENT HISTOGENESIS

Abstract

BACKGROUND: The KIAA1549:BRAF fusion (K-B fusion) gene has been considered a driver genetic events and a useful diagnostic marker in pilocytic astrocytomas (PA). However B-K gene fusion has been reported at low frequency in adult diffuse gliomas in association with IDH mutations. To further evaluate the possible occurrence of the B-K gene in non-PA tumors, we investigated the presence of the fusion gene in a series of 69 pediatric brain neoplasms of different histogenesis and grading. METHODS: Reverse-transcription polymerase chain reaction (RT-PCR) and subsequent sequencing. To further validate our findings we performed DNA-based methods as CNV and FISH. For CNV analysis, we used BRAF and KIAA specific primers for quantitative PCR in order to demonstrate the specific gain of the two genes, and for FISH analysis we used a commercially available probe. RESULTS: We detected B-K fusion gene in 5 out 34 (14,7%) non-PA primary tumors, i.e, 1 glioblastomas, 1 anaplastic astrocytoma, 1 anaplastic PXA, 1 ependymoma and 1 ATRT. Moreover, the fusion gene was present in 21 of 35 (63.6%) PAs, and out 3 (33%) WHO grade I gangliogliomas, a percentage overlapping previous studies on pediatric low grade gliomas. Both methods confirmed the presence of the B-K fusion gene but also indicate that the cells harboring the alteration in non-PAs neoplasms were less numerous compared to PAs. Screening for IDH, BRAFv600, and H3F3A mutations showed only one case with K27M-H3.3 mutation, which was not associated with B-K gene. CONCLUSIONS: Our study indicates that: 1) K-B fusion gene can be occasionally detected at low frequency in non-PA tumor of different histogenesis; 2) its occurrence in these neoplasms, probably, represents a random alteration related to genomic instability more than a driver molecular event, 3) its role as diagnostic marker outside the histological spectrum of pediatric low grade gliomas needs to be cautious. SECONDARY CATEGORY: Pediatrics.