Related Experiment Video
Updated: Jun 26, 2025
Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
Diffuse Gliomas with FGFR3::TACC3 Fusion: Morphological and Molecular Features and Classification Challenges
Elena Marastoni1, Davide Mulone1, Valeria Barresi1
1Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy.
Abstract:
FGFR3::TACC3 fusion is a driver, potentially targetable, genetic alteration identified in approximately 4% of high-grade diffuse gliomas and rare cases with low-grade histology. Herein, we review the genetic and epigenetic features of these tumors and highlight the challenges in their classification and grading. Diffuse gliomas with FGFR3::TACC3 fusion display unique histopathological and molecular features, including an oligodendroglioma-like appearance, calcifications, and CD34 extravascular immunoreactivity. High-grade tumors exhibit molecular alterations and a DNA methylation profile typical of glioblastoma, suggesting that they may represent a subtype clinically characterized by a slightly better prognosis. Tumors with low-grade morphology are genetically and epigenetically heterogeneous. Some, exclusive to adults, have molecular alterations typical of glioblastoma, although most do not match any methylation classes, using version 12.5 of the Heidelberg classifier. Another group, which mostly affects children or adolescents, lacks the molecular features of glioblastoma and has a DNA methylation profile similar to that of low-grade glioneuronal tumors. In conclusion, diffuse gliomas with FGFR3::TACC3 fusion do not constitute a distinct nosological entity, owing to their genetic and epigenetic diversity. Further studies are warranted to clarify the biological aggressiveness of tumors with low-grade histology to refine the grading and determine the optimal treatment strategy.
Insights
Diffuse gliomas with FGFR3::TACC3 fusion present diverse genetic and epigenetic profiles, complicating classification. These tumors, while sharing some features, do not form a single distinct entity requiring further study for optimal grading and treatment.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Cancer Genetics
Background:
- FGFR3::TACC3 fusion is a driver alteration in ~4% of high-grade diffuse gliomas.
- These gliomas exhibit unique histopathological and molecular features, including oligodendroglioma-like appearance and calcifications.
Purpose of the Study:
- To review the genetic and epigenetic features of diffuse gliomas with FGFR3::TACC3 fusion.
- To highlight challenges in classifying and grading these heterogeneous tumors.
- To explore potential therapeutic targets and refine treatment strategies.
Main Methods:
- Review of genetic and epigenetic alterations in diffuse gliomas with FGFR3::TACC3 fusion.
- Histopathological and molecular analysis, including DNA methylation profiling (Heidelberg classifier v12.5).
- Clinical data review for prognostic and therapeutic insights.
Main Results:
- High-grade tumors show glioblastoma-like profiles, suggesting a distinct subtype with potentially better prognosis.
- Low-grade tumors are heterogeneous: some adult cases resemble glioblastoma, while pediatric/adolescent cases align with low-grade glioneuronal tumors.
- Tumors often lack definitive classification within current methylation-based systems.
Conclusions:
- Diffuse gliomas with FGFR3::TACC3 fusion lack a distinct nosological entity due to genetic and epigenetic diversity.
- Further research is needed to clarify the biological aggressiveness of low-grade variants.
- Refined grading and optimal treatment strategies require additional investigation.
