FGFR1Mutations in Rosette-Forming Glioneuronal Tumors of the Fourth Ventricle

Abstract

Rosette-forming glioneuronal tumors (RGNTs) are rare glioneuronal tumors of the fourth ventricle region that preferentially affect young adults. Despite their histologic similarity with pilocytic astrocytomas (PAs), RGNTs do not harbor KIAA1549-BRAF fusions or BRAF mutations, which represent the most common genetic alteration in PAs. Recently, mutations affecting the hotspot codons Asn546 and Lys656 of fibroblast growth factor receptor 1 (FGFR1) have been described in PAs. They are considered to be the most frequent mechanism of mitogen-activated protein kinase activation, alternative to KIAA1549-BRAF fusion and BRAF mutations. To uncover possible molecular similarities between RGNTs and PAs, we performed a mutational study of FGFR1 in 8 RGNTs. An FGFR1 N546K mutation and an FGFR1 K656E mutation were found in the tumors of 2 patients. Notably, the patient with an FGFR1 K656E mutated RGNT had undergone a resection of a diencephalic pilocytic astrocytoma with pilomyxoid features 5 years before the discovery of the fourth ventricle tumor; the mutational analysis uncovered the presence of the same FGFR1 K656E mutation in the diencephalic tumor. These results indicate that, in addition to histologic similarities, at least a subgroup of RGNTs may show close molecular relationships with PAs. Whether FGFR1 mutated RGNTs represent a specific subset of this rare tumor entity remains to be determined.

Dysembryoplastic Neuroepithelial Tumor of the Septum Pellucidum and the Supratentorial Midline

“…10 In particular, data regarding the possible presence of BRAF mutations, KIAA1549-BRAF fusion, and FGFR1 mutations frequently identified in pilocytic astrocytomas and in other glioneuronal tumors, 14,15,17 or MYB and MYBL1 alterations observed in pediatric LGG, 14 are to date not available.…”

“…17 In pilocytic astrocytoma, these mutations are considered to represent a mechanism of MAPK pathway activation alternative to KIAA1549-BRAF fusions and BRAF mutations. FGFR1 mutations have been mainly found in midline tumors, which presumably originate from the periventricular white matter.…”

“…We screened the hotspot codon 600 (exon 15) of the BRAF gene and hotspot codons 546 and 656 of the FGFR1 gene for mutations using a pyrosequencing assay as reported in detail elsewhere. 16,17 As a positive control for BRAF V600E , DNA from a mutated melanoma brain metastasis was used.…”

Genomic Analysis in the Practice of Surgical Neuropathology: The Emory Experience

“…30,42,43 Some cases of RGNT have been described with PIK3CA mutations. 44 NTRK2 fusion events have been reported in PAs.…”

“…As stated previously, ETMRs are typified by a focal gain at 19q13. 42,54 and they can also be diagnosed by documenting LIN28A overexpression by immunohistochemistry. 62 In our practice, we rely on the MIP array to detect the focal gain of 19q13.42 rather than LIN28A expression.…”