Abstract 386P
Background
Gliomas belong to the most numerous primary malignancies of the central nervous system. Patients with high grade gliomas have a poor prognosis with limited survival despite multimodal anticancer therapy. Introduction of advanced sequencing techniques have identified gene rearrangements encoding oncogenic fusions that are potential therapeutic targets in gliomas. We used a comprehensive NGS assay to identify druggable oncogene fusions in our glioma patients with potential for clinical trial involvement.
Methods
Glioma patients treated by neurosurgery between 2017 and 2019 were enrolled. Current WHO classification was used for histopathological evaluation. Fusion transcript detection and mutation analysis in FFPE tissue were done by TruSight Tumor 170 (Illumina, USA). Additionally, fusion transcripts were detected by two FusionPlex kits - Solid Tumor and Comprehensive Thyroid and Lung (ArcherDX, Boulder, USA).
Results
Oncogene fusions were detected in 33 patients (pts) - KIAA1549-BRAF fusion in 13 pts. (9 pilocytic astrocytomas, 1 anaplastic pilocytic astrocytoma, 1 pilomyxoid astrocytoma, 1 diffuse leptomeningealglioneuronal tumour, 1 ganglioglioma), FGFR fusions (FGFR1-TACC1, FGFR2-CTNNA3, FGFR3-TACC3, FGFR3-CKAP5, FGFR3-AMBRA1) in 10 pts. (4 glioblastomas, 2 anaplastic astrocytomas, 1 anaplastic oligodendroglioma, 1 diffuse astrocytoma, 1 pilocytic astrocytoma), MET fusions (PTPRZ1-MET, SRPK2-MET) in 2 glioblastomas, C11orf95-RELA fusions in 2 anaplastic ependymomas, EGFR-SEPT14 in 2 glioblastomas, SRGAP3-BRAF and RAF1-TRIM2 in 2 pilocytic astrocytomas, EWSR1-PALGL1 in low-grade glial tumour not-otherwise specified, and TERT-ALK in glioneuronal tumour with neuropil-like islands. A clinical trial with pan-FGFR inhibitor was considered for FGFR rearranged tumours. ALK inhibition was considered for the patient with an ALK fusion.
Conclusions
NGS techniques bring relevant information about tumour molecular alterations into multimodal management of glioma patients. Those with tumours harbouring targetable gene fusions can benefit from clinical trials, especially in the case of limited or exhausted standard therapy. Supported by Charles University Research Fund (Progres Q39) and MH CZ-DRO (University Hospital Plzen-FNPl, 00669806).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Supported by Charles University Research Fund (Progres Q39) and MH CZ-DRO (University Hospital Plzen-FNPl, 00669806).
Disclosure
All authors have declared no conflicts of interest.