Open AccessReview
Diffuse Gliomas with FGFR3::TACC3 Fusion: Morphological and Molecular Features and Classification Challenges
by
Elena Marastoni
Elena Marastoni †,
Davide Mulone
Davide Mulone † and
Valeria Barresi
Valeria Barresi
Prof. Dr. Valeria Barresi has been Associate Professor of Pathological Anatomy (SSD MED/08) at the a [...]
Prof. Dr. Valeria Barresi has been Associate Professor of Pathological Anatomy (SSD MED/08) at the Department of Diagnostics and Public Health of the University of Verona since October 2018. She previously served as Associate Professor of Pathological Anatomy at the University of Messina (2018) and permanent university researcher at the University of Messina from 2008 to 2018. She earned her PhD in Clinical, Applied Oncology and Translational Research on Tumors. She obtained a national scientific qualification for Full Professor of Pathology in April 2020. She was a fellow at Johns Hopkins University, USA, and the University of Manchester, UK, studying the diagnostic pathology of tumours of the central nervous system. Since October 2022 she has been the Chair of the Italian Neuropathology Group of the Italian Society of Pathological Anatomy and Cytopathology, and in 2023 she participated in drafting the guidelines of the Italian Association of Medical Oncology for "Primitive Cerebral Neoplasms". Her main research interests include molecular classification and prognostic factors in central nervous system tumors and epithelial mesenchymal transition in colorectal cancer.
*
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.
Submission received: 6 April 2024
/
Revised: 21 April 2024
/
Accepted: 22 April 2024
/
Published: 25 April 2024
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.
Share and Cite
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
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details
here.
Article Metrics
Article Access Statistics
For more information on the journal statistics, click
here.
Multiple requests from the same IP address are counted as one view.