ArticleNeuro-oncology practice2021
FGFR3 overexpression is a useful detection tool for FGFR3 fusions and sequence variations in glioma.
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16 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- EANO guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection.Neuro-oncology · 2023Guideline
- Article
- Clinical and Genetic Landscape of Glioblastoma, IDH-Wildtype With FGFR Gene Family Alterations.Cancer science · 2026Article
- Myxoid glioneuronal tumor of the septum pellucidum with concurrent dualFrontiers in oncology · 2026Article
- Diffuse glioma withRadiology case reports · 2025Article
- Fibroblast growth factor receptor alterations and resistance mechanisms in the treatment of pediatric solid tumors.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Diffuse Gliomas withCancers · 2024Review
- RT-PCR assay to detectNeuro-oncology practice · 2024Article
- FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions.Nature reviews. Clinical oncology · 2024Review
- The landscape of cancer-associated transcript fusions in adult brain tumors: a longitudinal assessment in 140 patients with cerebral gliomas and brain metastases.Frontiers in oncology · 2024Article
- Diffuse Gliomas with FGFR3-TACC3 Fusions: Oncogenic Mechanisms, Hallmarks, and Therapeutic Perspectives.Cancers · 2023Review
- Clinico-pathological and epigenetic heterogeneity of diffuse gliomas with FGFR3::TACC3 fusion.Acta neuropathologica communications · 2023Article
- Clinical updates on gliomas and implications of the 5th edition of the WHO classification of central nervous system tumors.Frontiers in oncology · 2023Article
- FGFR1-4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer.International journal of molecular sciences · 2022Article
- FGFR3-TACCs3 Fusions and Their Clinical Relevance in Human Glioblastoma.International journal of molecular sciences · 2022Review
- The oncogenic fusion landscape in pediatric CNS neoplasms.Acta neuropathologica · 2022Review
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFibroblast growth factor receptor (FGFR) inhibitors are currently used in clinical development. A subset of glioblastomas carries gene fusion of FGFR3 and transforming acidic coiled-coil protein 3. The prevalence of other FGFR3 alterations in glioma is currently unclear.
methodsWe performed RT-PCR in 101 glioblastoma samples to detect FGFR3-TACC3 fusions ("RT-PCR cohort") and correlated results with FGFR3 immunohistochemistry (IHC). Further, we applied FGFR3 IHC in 552 tissue microarray glioma samples ("TMA cohort") and validated these results in two external cohorts with 319 patients. Gene panel sequencing was carried out in 88 samples ("NGS cohort") to identify other possible FGFR3 alterations. Molecular modeling was performed on newly detected mutations.
resultsIn the "RT-PCR cohort," we identified FGFR3-TACC3 fusions in 2/101 glioblastomas. Positive IHC staining was observed in 73/1024 tumor samples of which 10 were strongly positive. In the "NGS cohort," we identified FGFR3 fusions in 9/88 cases, FGFR3 amplification in 2/88 cases, and FGFR3 gene mutations in 7/88 cases in targeted sequencing. All FGFR3 fusions and amplifications and a novel FGFR3 K649R missense mutation were associated with FGFR3 overexpression (sensitivity and specificity of 93% and 95%, respectively, at cutoff IHC score > 7). Modeling of these data indicated that Tyr647, a residue phosphorylated as a part of FGFR3 activation, is affected by the K649R mutation.
conclusionsFGFR3 IHC is a useful screening tool for the detection of FGFR3 alterations and could be included in the workflow for isocitrate dehydrogenase (IDH) wild-type glioma diagnostics. Samples with positive FGFR3 staining could then be selected for NGS-based diagnostic tools.
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