Comprehensive genetic characterization of rosette‐forming glioneuronal tumors: independent component analysis by tissue microdissection

Kitamura, Yohei; Komori, Takashi; Shibuya, Makoto; Ohara, Kentaro; Saito, Yuko; Hayashi, Shoryo; Sasaki, Aya; Nakagawa, Eiji; Tomio, Ryosuke; Kakita, Akiyoshi; Nakatsukasa, Masashi; Yoshida, Kazunari; Sasaki, Hidenao

doi:10.1111/bpa.12468

Cited by 23 publications

(10 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous reports have indicated that the incidence of an FGFR1 mutation is 5.2%-6.7% in PA, 1,10 36.4% in DNT, 20 10% in oligodendroglioma, 20 and 46.2%-50% in rosette-forming glioneuronal tumor. 5,14 Our results suggest that FGFR1 mutation is also observed in pediatric and young adult cases of DA and PMA. All 4 cases harboring an FGFR1 mutation in our study were located in the thalamus and hypothalamus, which is consistent with previous reports of PA. 10 Although the FGFR1 mutation is associated with a poor prognosis in PA, 1 our cases had a significantly different outcome, suggesting clinical heterogeneity with respect to the FGFR1 mutation.…”

Section: Clinical Characteristics Of Lggs With An Fgfr1 Mutationmentioning

confidence: 51%

Association of the FGFR1 mutation with spontaneous hemorrhage in low-grade gliomas in pediatric and young adult patients

Ishi

Yamaguchi

Hatanaka

et al. 2021

Journal of Neurosurgery

View full text Add to dashboard Cite

OBJECTIVEThe authors aimed to investigate genetic alterations in low-grade gliomas (LGGs) in pediatric and young adult patients presenting with spontaneous hemorrhage.METHODSPatients younger than 30 years of age with a pathological diagnosis of World Health Organization (WHO) grade I or II glioma and who had undergone treatment at the authors’ institution were retrospectively examined. BRAF V600E, FGFR1 N546/K656, IDH1 R132, IDH2 R172, and KIAA1549-BRAF (K-B) fusion genetic alterations were identified, and the presence of spontaneous tumoral hemorrhage was recorded.RESULTSAmong 66 patients (39 with WHO grade I and 27 with grade II tumors), genetic analysis revealed K-B fusion in 18 (27.3%), BRAF V600E mutation in 14 (21.2%), IDH1/2 mutation in 8 (12.1%), and FGFR1 mutation in 4 (6.1%). Spontaneous hemorrhage was observed in 5 patients (7.6%); 4 of them had an FGFR1 mutation and 1 had K-B fusion. Univariate analysis revealed a statistically significant association of an FGFR1 mutation and a diencephalic location with spontaneous hemorrhage. Among 19 diencephalic cases including the optic pathway, hypothalamus, and thalamus, an FGFR1 mutation was significantly associated with spontaneous hemorrhage (p < 0.001). Four FGFR1 mutation cases illustrated the following results: 1) a 2-year-old female with pilomyxoid astrocytoma (PMA) harboring the FGFR1 K656E mutation presented with intraventricular hemorrhage (IVH); 2) a 6-year-old male with PMA harboring FGFR1 K656E and D652G mutations presented with intratumoral hemorrhage (ITH); 3) a 4-year-old female with diffuse astrocytoma harboring FGFR1 K656M and D652G mutations presented with IVH; and 4) a young adult patient with pilocytic astrocytoma with the FGFR1 N546K mutation presented with delayed ITH and IVH after 7 years of observation.CONCLUSIONSAlthough the mechanism remains unclear, the FGFR1 mutation is associated with spontaneous hemorrhage in pediatric and young adult LGG.

show abstract

Section: Clinical Characteristics Of Lggs With An Fgfr1 Mutationmentioning

confidence: 51%

Association of the FGFR1 mutation with spontaneous hemorrhage in low-grade gliomas in pediatric and young adult patients

Ishi

Yamaguchi

Hatanaka

et al. 2021

Journal of Neurosurgery

View full text Add to dashboard Cite

show abstract

“…Some alterations are pathognomonic for a tumor entity as SLC44A1‐PRKCA fusion gene for PGNT ; others are associated with two or more entities, as FGFR1 mutations associated at least with DNET, rosette forming glioneuronal tumor and pilocytic astrocytoma . It seems crucial to put our Case 1 into the molecular context of glioneuronal tumors . No fusions were detected involving PRKCA, BRAF , FGFR1, FGFR2, FGFR3 , MYB1 or MYBL1 genes although those genes were present in the capture panel of the TruSight RNA fusion kit.…”

Section: Discussionmentioning

confidence: 95%

EWSR1‐PATZ1 gene fusion may define a new glioneuronal tumor entity

et al. 2018

View full text Add to dashboard Cite

We investigated the challenging diagnostic case of a ventricular cystic glioneuronal tumor with papillary features, by RNA sequencing using the Illumina TruSight RNA Fusion panel. We did not retrieve the SLC44A1-PRKCA fusion gene specific for papillary glioneuronal tumor, but an EWSR1-PATZ1 fusion transcript. RT-PCR followed by Sanger sequencing confirmed the EWSR1-PATZ1 fusion. It matched with canonic EWSR1 fusion oncogene, juxtaposing the entire N-terminal transcriptional activation domain of EWSR1 gene and the C-terminal DNA binding domain of a transcription factor gene, PATZ1. PATZ1 protein belongs to the BTB-ZF (broad-complex, tramtrack and bric-à-brac -zinc finger) family. It directly regulates Pou5f1 and Nanog and is essential to maintaining stemness by inhibiting neural differentiation. EWSR1-PATZ1 fusion is a rare event in tumors: it was only reported in six round cell sarcomas and in three gliomas of three exclusively molecular studies. The first reported glioma was a BRAF negative ganglioglioma, the second a BRAF negative glioneuronal tumor, not otherwise specified and the third, very recently reported, a high grade glioma, not otherwise specified. In our study, forty BRAF negative gangliogliomas were screened by FISH using EWSR1 break-apart probes. We performed methylation profiling for the index case and for seven out of the ten FISH positive cases. The index case clustered apart from other pediatric low grade glioneuronal entities, and specifically from the well-defined ganglioglioma methylation group. An additional pediatric intraventricular ganglioglioma clustered slightly more closely with ganglioglioma, but showed differences from the main ganglioglioma group and similarities with the index case. Both cases harbored copy number variations at the PATZ1 locus. EWSR1-PATZ1 gene fusion might define a new type of glioneuronal tumors, distinct from gangliogliomas.

show abstract

“…The FGFR1 gene on chromosome 8p11.23 has emerged as a recurrently altered oncogene in a diverse spectrum of primary glial and glioneuronal tumor entities including DNT [ 31 , 33 , 34 , 40 , 41 ], RGNT [ 14 , 19 , 22 , 36 ], EVN [ 38 ], pilocytic astrocytoma [ 3 , 18 , 27 , 34 , 44 ], high-grade astrocytoma with piloid features [ 2 , 32 ], and H3 K27M-mutant diffuse midline glioma [ 24 ]. Notably, FGFR1 alterations are not commonly found in IDH-wildtype glioblastoma in adults, IDH-mutant astrocytoma, IDH-mutant and 1p/19q-codeleted oligodendroglioma, H3.3 G34-mutant diffuse hemispheric glioma, ganglioglioma, polymorphous low-grade neuroepithelial tumor of the young (PLNTY), papillary glioneuronal tumor, myxoid glioneuronal tumor, multinodular and vacuolating neuronal tumor, diffuse leptomeningeal glioneuronal tumor (DLGNT), central neurocytoma, and ependymomas of any location or subtype [ 5 , 6 , 8 , 9 , 16 , 17 , 23 , 24 , 26 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of diverse low-grade neuroepithelial tumors with FGFR1 alterations reveals a distinct molecular signature of rosette-forming glioneuronal tumor

Lucas

Gupta

Doo

et al. 2020

acta neuropathol commun

View full text Add to dashboard Cite

The FGFR1 gene encoding fibroblast growth factor receptor 1 has emerged as a frequently altered oncogene in the pathogenesis of multiple low-grade neuroepithelial tumor (LGNET) subtypes including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumor (DNT), rosette-forming glioneuronal tumor (RGNT), and extraventricular neurocytoma (EVN). These activating FGFR1 alterations in LGNET can include tandem duplication of the exons encoding the intracellular tyrosine kinase domain, in-frame gene fusions most often with TACC1 as the partner, or hotspot missense mutations within the tyrosine kinase domain (either at p.N546 or p.K656). However, the specificity of these different FGFR1 events for the various LGNET subtypes and accompanying genetic alterations are not well defined. Here we performed comprehensive genomic and epigenomic characterization on a diverse cohort of 30 LGNET with FGFR1 alterations. We identified that RGNT harbors a distinct epigenetic signature compared to other LGNET with FGFR1 alterations, and is uniquely characterized by FGFR1 kinase domain hotspot missense mutations in combination with either PIK3CA or PIK3R1 mutation, often with accompanying NF1 or PTPN11 mutation. In contrast, EVN harbors its own distinct epigenetic signature and is characterized by FGFR1-TACC1 fusion as the solitary pathogenic alteration. Additionally, DNT and pilocytic astrocytoma are characterized by either kinase domain tandem duplication or hotspot missense mutations, occasionally with accompanying NF1 or PTPN11 mutation, but lacking the accompanying PIK3CA

show abstract

Comprehensive genetic characterization of rosette‐forming glioneuronal tumors: independent component analysis by tissue microdissection

Cited by 23 publications

References 34 publications

Association of the FGFR1 mutation with spontaneous hemorrhage in low-grade gliomas in pediatric and young adult patients

Association of the FGFR1 mutation with spontaneous hemorrhage in low-grade gliomas in pediatric and young adult patients

EWSR1‐PATZ1 gene fusion may define a new glioneuronal tumor entity

Comprehensive analysis of diverse low-grade neuroepithelial tumors with FGFR1 alterations reveals a distinct molecular signature of rosette-forming glioneuronal tumor

Contact Info

Product

Resources

About