Varied histomorphology and clinical outcomes of FGFR3-TACC3 fusion gliomas

• Published in: Neurosurgical focus Vol. 53; no. 6; p. E16
• Main Authors: McDonald, Malcolm F, Athukuri, Prazwal, Anand, Adrish, Gopakumar, Sricharan, Jalali, Ali, Patel, Akash J, Rao, Ganesh, Goodman, J Clay, Lu, Hsiang-Chih, Mandel, Jacob J
• Format: Journal Article
• Language: English
• Published: United States 01.12.2022
• Subjects: Glioblastoma; Glioma - genetics; Glioma - surgery; Humans; Microtubule-Associated Proteins; Mutation; Protein Kinase Inhibitors; Receptor, Fibroblast Growth Factor, Type 3 - genetics; glioma; glioblastoma; pathology; FGFR3-TACC3; IDH–wild-type GBM
• ISSN: 1092-0684; 1092-0684
• DOI: 10.3171/2022.9.FOCUS22420

Targeted therapies for driver gene fusions in cancers have yielded substantial improvements in care. Here, the authors outline a case series of 6 patients with FGFR3-TACC3 fusion in primary brain tumors ranging from polymorphous low-grade neuroepithelial tumor of the young to papillary glioneuronal tumors and glioblastoma (GBM). Previous studies indicated the FGFR3-TACC3 fusion provides survival benefit to GBM patients. Consistent with this, 2 patients with GBM had unexpectedly good outcomes and survived for 5 and 7 years, respectively. In contrast, 2 patients with initially lower graded tumors survived only 3 years and 1 year, respectively. One patient received erdafitinib, a targeted FGFR inhibitor, for 3 months at late disease recurrence and no response was seen. There were varied histomorphological features, including many cases that lacked the characteristic FGFR3-TACC3 pathology. The findings of this cohort suggest that molecular testing is justified, even for glioma cases lacking classic histopathological signatures. Currently, FGFR3-TACC3 fusion gliomas are often classified on the basis of histopathological features. However, further research is needed to examine whether IDH1/2-wild-type tumors with FGFR3-TACC3 fusion should be classified as a subtype on the basis of this molecular fusion. Because patients with IDH1/2-wild-type GBM with FGFR3-TACC3 fusion have improved survival, routine molecular testing for this mutation in patients enrolled in clinical trials and subsequent stratification may be warranted.