RNA fusion transcript panel identifies diverse repertoire of fusions in adult glioma patients with therapeutic implications

Abstract

Background Recurrent gliomas are therapeutically challenging diseases with few treatment options available. One area of potential therapeutic vulnerability is the presence of targetable oncogenic fusion proteins. Methods To better understand the clinical benefit of routinely testing for fusion proteins in adult glioma patients, we performed a retrospective review of 647 adult patients with glioma who underwent surgical resection at our center between August 2017-May 2021 and whose tumors were analyzed with an in-house fusion transcript panel (FTP). Results Fifty-two patients (8%) were found to harbor a potentially targetable fusion with eleven (21%) of these patients receiving treatment with a fusion targeted inhibitor. The targetable genes found to be involved in a fusion included FGFR3, MET, EGFR, NTRK1, NTRK2, BRAF, ROS1, and PIK3CA. Conclusions This analysis demonstrates that routine clinical testing for gene fusions identifies a diverse repertoire of potential therapeutic targets in adult patients with glioma and can offer rational therapeutic options for patients with recurrent disease.

Next generation sequencing of high-grade adult-type diffuse glioma in the Netherlands: interlaboratory variation in the primary diagnostic and recurrent setting

“…For example, about half of the centers test for gene fusions (60%) and tumor mutational burden (40%). Although the occurrence of targetable gene fusions in glioblastoma is low and treatment effectiveness in the context of expediency is still being investigated, patient selection for potential trial participation is reduced when testing is omitted [ 20 , 21 ].…”