Infiltrating gliomas with FGFR alterations: Histologic features, genetic alterations, and potential clinical implications

Article type: Research Article

Authors: Dono, Antonio^{a; b} | El Achi, Hanadi^a | Bundrant, Bethany E.^a | Goli, Puneetha S.^c | Zhu, Ping^b | Ozkizilkaya, Hanim I.^d | Esquenazi, Yoshua^{b; e; f; *} | Ballester, Leomar Y.^{d; g; *}

Affiliations: [a] Department of Pathology and Laboratory Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA | [b] Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA | [c] Rice University, Houston, TX, USA | [d] Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA | [e] Memorial Hermann Hospital-TMC, Houston, TX, USA | [f] Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA | [g] Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence: [*] Corresponding authors: Leomar Y. Ballester, Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Ave, Unit 85, Houston, TX 77030, USA. E-mail: lyballester1@mdanderson.org. Yosuha Esquenazi, Center for Precision Health, School of Biomedical Informatics, Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston Mischer Neuroscience Institute, 6400 Fannin, Suite 2800, Houston, TX 77030, USA. E-mail: yoshua.esquenazilevy@uth.tmc.edu.

Abstract: BACKGROUND: Fibroblast growth factor receptors (FGFRs) are frequently altered in cancers and present a potential therapeutic avenue. However, the type and prevalence of FGFR alterations in infiltrating gliomas (IGs) needs further investigation. OBJECTIVE: To understand the prevalence/type of FGFR alterations in IGs. METHODS: We reviewed clinicopathologic and genomic alterations of FGFR-mutant gliomas in a cohort of 387 patients. Tumors were examined by DNA next-generation sequencing for somatic mutations with a panel interrogating 205-genes. For comparison, cBioPortal databases were queried to identify FGFR-altered IGs. RESULTS: Fourteen patients (3.6%) with FGFR-mutant tumors were identified including 11 glioblastomas, Isocitrate dehydrogenase (IDH) – wildtype (GBM-IDH-WT), 2 oligodendrogliomas, and 1 astrocytoma IDH-mutant. FGFR-altered IGs showed endocrinoid capillaries, microvascular proliferation, necrosis, oligodendroglioma-like cells, fibrin thrombi, microcalcifications, and nodular growth. FGFR3 was the most commonly altered FGFR gene (64.3%). The most common additional mutations in FGFR-altered IGs were TERTp, CDKN2A/B, PTEN, CDK4, MDM2, and TP53. FGFR3 alterations were only observed in GBM-IDH-WT. EGFR alterations were rarely identified in FGFR3-altered gliomas. CONCLUSIONS: Histologic features correlate with FGFR alterations in IGs. FGFR3-TACC3 fusion and FGFR3 amplification are the most common FGFR alterations in IGs. FGFR alterations are a rare, but potentially viable, therapeutic target in asubset of IGs.

Keywords: Infiltrating glioma, FGFR1, FGFR2, FGFR3, glioblastoma, oligodendroglioma, FGFR3-TACC3, targeted therapy

DOI: 10.3233/CBM-220041

Journal: Cancer Biomarkers, vol. 36, no. 2, pp. 117-131, 2023