Frequent FGFR1 hotspot alterations in driver-unknown low-grade glioma and mixed neuronal-glial tumors.
FGFR1
Immunohistochemistry
Low-grade glioma
Mixed neuronal glial tumor
Pyrosequencing
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
received:
23
09
2021
accepted:
25
12
2021
pubmed:
13
1
2022
medline:
22
3
2022
entrez:
12
1
2022
Statut:
ppublish
Résumé
Low-grade gliomas (LGG) and mixed neuronal-glial tumors (MNGT) show frequent MAPK pathway alterations. Oncogenic fibroblast growth factor receptor 1 (FGFR1) tyrosinase kinase domain has been reported in brain tumors of various histologies. We sought to determine the frequency of FGFR1 hotspot mutations N546 and K656 in driver-unknown LGG/MNGT and examined FGFR1 immunohistochemistry as a potential tool to detect those alterations. We analyzed 476 LGG/MNGT tumors for KIAA-1549-BRAF fusion, IDH1/2, TERT promotor, NF1, H3F3A and the remaining cases for FGFR1 mutation frequency and correlated FGFR1 immunohistochemistry in 106 cases. 368 of 476 LGG/MNGT tumors contained non-FGFR1 alterations. We identified 9 FGFR1 p.N546K and 4 FGFR1 p.K656E mutations among the 108 remaining driver-unknown samples. Five tumors were classified as dysembryoplastic neuroepithelial tumor (DNT), 4 as pilocytic astrocytoma (PA) and 3 as rosette-forming glioneuronal tumor (RGNT). FGFR1 mutations were associated with oligodendroglia-like cells, but not with age or tumor location. FGFR1 immunohistochemical expression was observed in 92 cases. FGFR1 immunoreactivity score was higher in PA and DNT compared to diffuse astrocytoma, but no correlation between FGFR1 mutation in tumors and FGFR1 expression level was observed. FGFR1 hotspot mutations are the fifth most prevailing alteration in LGG/MNGT. Performing FGFR1 sequencing analysis in driver-unknown low-grade brain tumors could yield up to 12% FGFR1 N546/K656 mutant cases.
Identifiants
pubmed: 35018490
doi: 10.1007/s00432-021-03906-x
pii: 10.1007/s00432-021-03906-x
pmc: PMC8930952
doi:
Substances chimiques
FGFR1 protein, human
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 1
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
857-866Informations de copyright
© 2022. The Author(s).
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