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), and PDGFRA fusions (n = 1). Gene fusions were consistently observed in both IDH-wildtype and IDH-mutant glioblastomas (8.8% and 9.4%, p = 1.000). PTPRZ1–MET fusion was the only fusion that genetically resembled secondary glioblastomas (i.e., high frequency of IDH mutation, ATRX loss, TP53 mutation, and absence of EGFR amplification), whereas other gene fusion types were similar to primary glioblastomas (i.e., high frequency of IDH-wildtype, TERT mutation, EGFR amplification, and PTEN mutation). In IDH-wildtype glioblastoma patients, multivariable analysis revealed that the PTPRZ1–MET fusion 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 of CCDC6–RET fusion 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.

致癌基因融合已在弥漫性胶质瘤中报道，可作为潜在的治疗靶标。在这里，我们使用下一代测序分析（Illumina TruSight Tumor 170面板）分析了2017年至2019年收集的356例弥漫性神经胶质瘤，以评估基因融合的临床，病理和遗传特征。我们发现53例胶质母细胞瘤病例具有以下致癌基因融合：MET（n  = 18），EGFR（n  = 14），FGFR（n  = 12），NTRK（n  = 5），RET（n  = 2），AKT3（n  = 1）和PDGFRA融合（n  = 1）。在IDH野生型和IDH突变的胶质母细胞瘤中均观察到基因融合（8.8％和9.4％，p  = 1.000）。PTPRZ1-MET融合蛋白是唯一在遗传上与继发性胶质母细胞瘤相似的融合体（即IDH突变频率高，ATRX丢失，TP53突变和EGFR扩增缺失），而其他基因融合类型与原发性胶质母细胞瘤相似（即高频的IDH -wildtype，TERT突变，EGFR扩增和PTEN突变）。在IDH中-wildtype胶质母细胞瘤患者中，多变量分析表明，PTPRZ1 - MET融合用差的无进展生存相关（HR [95％CI]：5.42（1.72-17.05），p  = 0.004）。此外，我们描述了CCDC6 – RET胶质瘤融合的两个新病例。总的来说，我们的发现表明可靶向的基因融合与侵略性生物学行为有关，并且可以帮助神经胶质瘤患者的临床治疗策略。