Glioblastomas harboring gene fusions detected by next-generation sequencing

Oncogenic gene fusions have been reported in diffuse gliomas and may serve as potential therapeutic targets. Here, using next-generation sequencing analysis (Illumina TruSight Tumor 170 panel), we analyzed a total of 356 diffuse gliomas collected from 2017 to 2019 to evaluate clinical, pathological, and genetic features of gene fusion. We found 53 cases of glioblastomas harboring the following oncogenic gene fusions:MET(n = 18),EGFR(n = 14),FGFR(n = 12),NTRK(n = 5),RET(n = 2),AKT3(n = 1), andPDGFRAfusions (n = 1). Gene fusions were consistently observed in bothIDH-wildtype andIDH-mutant glioblastomas (8.8% and 9.4%,p = 1.000).PTPRZ1-METfusion was the only fusion that genetically resembled secondary glioblastomas (i.e., high frequency ofIDHmutation,ATRXloss,TP53mutation, and absence ofEGFRamplification), whereas other gene fusion types were similar to primary glioblastomas (i.e., high frequency ofIDH-wildtype,TERTmutation,EGFRamplification, andPTENmutation). InIDH-wildtype glioblastoma patients, multivariable analysis revealed that thePTPRZ1-METfusion was associated with poor progression-free survival (HR [95% CI]: 5.42 (1.72-17.05),p = 0.004). Additionally, we described two novel cases ofCCDC6-RETfusion in glioma. Collectively, our findings indicate that targetable gene fusions are associated with aggressive biological behavior and can aid the clinical treatment strategy for glioma patients.