Identification of the clinical and genetic characteristics of gliomas with gene fusions by integrated genomic and transcriptomic analysis

Abstract The identification of oncogenic gene fusions in diffuse gliomas may serve as potential therapeutic targets and prognostic indicators, representing a novel strategy for treating gliomas consistent with the principles of personalized medicine. This study identified detectable oncogene fusions in glioma patients through an integrated analysis of genomic and transcriptomic data, which encompassed whole exon sequencing and next-generation RNA sequencing. Additionally, this study also conducted a comparison of the genetic characteristics, tumor microenvironment, mutation burden and survival between glioma patients with or without gene fusions. A total of 68 glioma patients were enrolled in this study, including glioblastoma (GBM), low grade glioma (LGG) and diffuse midline glioma (DMG). 14 cases of GBM patients (51.9%, 14/27) were found to harbor the following 70 oncogenic gene fusions: ROS1 (n = 8), NTRK (n = 5), KIF5 (n = 5), RET (n = 3) and other infrequent gene fusions (n = 49). A total of 11 gene fusions were identified in 8 LGG patients (32.0%, 8/25) and seven gene fusions were identified in one DMG patient (16.7%, 1/6). In GBM patient group, five genes including HOXA3, ACTB, CDK5, GNA12 and CARD11 exhibited a statistically significant higher copy number amplification frequency in the GBM group without gene fusions compared to that in the GBM group with gene fusions. In LGG patient group, CDK5 gene was also found to exhibit a statistically significant higher amplification frequency in the LGG group without gene fusions. Additionally, KMT2D exhibited a statistically significant higher mutation frequency in the LGG group with gene fusions compared to that in the LGG group without gene fusions. Comparison of the other genetic characteristics including immune cell infiltration score, tumor mutation burden (TMB), and microsatellite instability (MSI). The results showed no statistically significant differences were observed between fusion and non-fusion group of GBM and LGG. The survival analysis revealed that GBM patients without gene fusions exhibited a longer median survival (737 days) compared to GBM patients with gene fusions (642 days), but without a statistical significancy. Our study has identified a set of gene fusions present in gliomas, including a number of novel gene fusions that have not been previously reported. We have also elucidated the underlying genetic characteristics of glioma with gene fusions. Collectively, our findings have the potential to inform future clinical treatment strategies for patients with glioma.