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Review

Diffuse Gliomas with FGFR3::TACC3 Fusion: Morphological and Molecular Features and Classification Challenges

by
Elena Marastoni
,
Davide Mulone
and
Valeria Barresi
*
Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2024, 16(9), 1644; https://doi.org/10.3390/cancers16091644
Submission received: 6 April 2024 / Revised: 21 April 2024 / Accepted: 22 April 2024 / Published: 25 April 2024
(This article belongs to the Special Issue Genomic, Epigenomic, and Transcriptomic Landscapes of Brain Cancers)

Simple Summary

FGFR3::TACC3 fusion is a driver, potentially targetable, alteration detected in approximately 4% of diffuse gliomas. Diffuse gliomas with FGFR3::TACC3 fusion (F3T3 gliomas) and high-grade histological features harbor molecular stigmata and the DNA methylation profile of glioblastoma, though they are associated with slightly longer patient survival. Histologically low-grade F3T3 gliomas are molecularly heterogeneous and likely comprise three epigenetic groups. One includes tumors, exclusive to adults, displaying genetic and epigenetic features of glioblastoma and potentially representing precursors of high-grade gliomas. The second group lacks the molecular features of glioblastoma and has an epigenetic profile similar to that of dysembryoplastic neuroepithelial tumors. Finally, tumors in the third group are epigenetically close to gangliogliomas. Owing to their genetic and epigenetic heterogeneity, F3T3 gliomas do not represent a distinct nosological entity. Further research is needed to clarify the prognosis, refine the grading, and determine the optimal treatment approaches for these tumors.

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.
Keywords: FGFR3::TACC3; FGFR3; glioma; PLNTY; glioblastoma; DNA methylation; ganglioglioma FGFR3::TACC3; FGFR3; glioma; PLNTY; glioblastoma; DNA methylation; ganglioglioma

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MDPI and ACS Style

Marastoni, E.; Mulone, D.; Barresi, V. Diffuse Gliomas with FGFR3::TACC3 Fusion: Morphological and Molecular Features and Classification Challenges. Cancers 2024, 16, 1644. https://doi.org/10.3390/cancers16091644

AMA Style

Marastoni E, Mulone D, Barresi V. Diffuse Gliomas with FGFR3::TACC3 Fusion: Morphological and Molecular Features and Classification Challenges. Cancers. 2024; 16(9):1644. https://doi.org/10.3390/cancers16091644

Chicago/Turabian Style

Marastoni, Elena, Davide Mulone, and Valeria Barresi. 2024. "Diffuse Gliomas with FGFR3::TACC3 Fusion: Morphological and Molecular Features and Classification Challenges" Cancers 16, no. 9: 1644. https://doi.org/10.3390/cancers16091644

APA Style

Marastoni, E., Mulone, D., & Barresi, V. (2024). Diffuse Gliomas with FGFR3::TACC3 Fusion: Morphological and Molecular Features and Classification Challenges. Cancers, 16(9), 1644. https://doi.org/10.3390/cancers16091644

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