Abstract 5746: Analysis of molecular characteristics of gliomas harboring gene fusions

Abstract

Abstract Background: Genotyping plays an important role in tumor diagnosis and prognosis. The 2016 central nervous system (CNS) WHO added molecular parameters to classify CNS tumors on the basis of routine histological features, but the characteristics of gene fusion variations have not been clarified in CNS tumors. Methods: In order to identify the characteristics of gene fusions in Chinese patients with CNS malignant tumors, we retrospectively analyzed the next-generation sequencing data of 234 patients (pts) with gene fusions. Results: According to WHO classification of CNS tumor, 121 pts (51.7%) were low-grade gliomas (LGG, grade I, II), and 113 pts (48.3%) were high-grade gliomas (HGG, grade III, IV). The age of pts with LGG (14.1 ± 16.1) was significantly lower than HGG pts (50.2 ± 17.4) (P<0.0001). There was no significant gender difference between them (P = 0.161). In the fusion map of pts with LGG, gene fusions of KIAA1549-BRAF (n=82, 67.7%) and FGFR3-TACC3 (n=7, 5.8%) occurred frequently. Meanwhile, there were 5.7% pts carrying BRAF fusions with other partners, and some other sporadic fusions. Among HGG cases, the most frequent gene fusion was FGFR3-TACC3 (n=36, 31.9%), followed by fusions in EGFR (n=22, 19.5%), MET (n=16, 14.2%), BRAF (n=8, 7.1%), ROS1 (n=5, 4.4%), and other sporadic genes. It can be seen that gene fusion characteristics varied from gliomas with different malignant degrees. KIAA1549-BRAF fusion tended to occur in LGG (67.7% vs. 2.7%, P < 0.0001) than HGG, and FGFR3-TACC3 tended to occur in HGG ( 31.9% vs. 5.8%, P< 0.0001) than LGG. In addition, FGFR3-TACC3 fusion pts were exclusive with IDH1/2 mutations, but tended to be co-mutate with TERT promoter variants (P<0.0001). IDH-mutation-positive glioma usually exhibit a better clinical result, while TERT promoter-mutated glioma predicts a poor outcome. We also found that 75% (12/16) of MET fusion-positive gliomas pts had TP53 co-coexisting and 56.3% (9/16) of MET fusion-positive gliomas pts co-occurred with MET amplification, while only 0.9% (1/105) of pts harboring other fusions were MET amplification positive. Meanwhile, 95.0% (21/22) of EGFR fusion-positive pts co-occurred with EGFR amplification. Conclusion: By comprehensively analyzing the gene fusion map of Chinese patients with gliomas, we found the gene fusion characteristics of LGG differed from that of HGG. These fusion features may be important molecular information for judging the grade of malignancy and prognosis of patients. Citation Format: Jidong Wang, Yushuai Han, Weiran Wang, Tonghui Ma. Analysis of molecular characteristics of gliomas harboring gene fusions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5746.