title: FGFR1 mutations 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.
authors.affiliation: From the Institut of Neuropathology, University of Bonn Medical Center, Bonn, Germany (MG, YAM, JH, TG, DD, AW, TP); Institut of Neurosurgery, Klinikum Duisburg, Duisburg, Germany (MS).
authors.forename: Marco
authors.initials: M
authors.lastname: Gessi
authors.forename: Yasmin Abdel
authors.initials: YA
authors.lastname: Moneim
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hammes
authors.forename: Tobias
authors.initials: T
authors.lastname: Goschzik
authors.forename: Martin
authors.initials: M
authors.lastname: Scholz
authors.forename: Dorota
authors.initials: D
authors.lastname: Denkhaus
authors.forename: Andreas
authors.initials: A
authors.lastname: Waha
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
mesh_terms: D000293:Adolescent; D000328:Adult; D002551:Cerebral Ventricle Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005260:Female; D020546:Fourth Ventricle / Q000378:metabolism / Q000473:pathology*; D018303:Ganglioglioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D055815:Young Adult
chemical_list: D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1