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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.
Cancers
|May 11, 2024
Summary
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.
