Abstract
Abstract Next-generation sequencing to identify fusion proteins is increasingly employed across oncology to identify therapeutic targets.1 The clinical relevance of detecting fusion transcripts is well described in the pediatric glioma population, but similar reports for adult patients are scant.2 The University of Pennsylvania Health System (UPHS) has implemented routine use of an RNA fusion transcript panel (ArcherDX, Boulder, CO) on resected brain tumors since August 2017. Here we report the results of this analysis for adult patients with gliomas and highlight potentially targetable fusions. Over the period of August 2017 through December 2019, fusion analysis was performed on resected gliomas of over 200 patients. Ninety-seven patients were found to have a detected fusion protein. Eighty-three of the 97 patients (86%) had glioblastoma and 14 (14%) had lower grade gliomas. A total of 26 unique fusions were found. The most common (n=55) was EGFRvIII. NTRK fusions were of special interest as FDA-approved agents are available for patients harboring this genetic alteration.3 We identified 8 patients (8%) with NTRK fusions including ARHGEFF2:NTRK1, BNA: NTRK1, BCR: NTRK2, PDE5A/NTRK2, SKAP2/NTRK2, and STRN: NTRK2. Several of these patients went on to receive TRK kinase inhibitors with clinical benefit. Of the 97 patients with a detected fusion, 24 (25%) were found to have a potentially targetable fusion other than EGFRvIII, with inhibitors available in clinical trials or as off-label therapy. These fusions included BRAF (n=5; BRAF: LHFPL3, KIAA1549:BRAF), FGFR (n=9; FGFR3:BRAP, FGFR3:RENBP, FGFR3:TACC3), MET (n=7; CAPZA2-MET, KLF12:MET, PTPRZ1:MET, ST7:MET), and ROS1 (n=3; DLL: ROS1, GOPC: ROS1). In sum, routine clinical use of an RNA-based fusion transcript panel for adult patients with glioma may allow for detection of therapeutically targetable alterations in a meaningful proportion of cases. Prospective trials are needed to determine whether targeting specific fusions is beneficial for adult patients with glioma.
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