Abstract LB-216: Frequent oncogenic tyrosine kinase gene fusions in supratentorial glioblastomas of young children

Abstract

Abstract Glioblastoma in infancy and early childhood is characterized by a more favorable outcome compared to older children. We have shown in previous studies that these tumors are characterized by a stable genome. The occurrence of tyrosine kinase gene fusions in glioblastomas of infancy may represent therapeutic targets. 50 glioblastomas (GBM) with supratentorial location occurring in children younger than four years were retrieved from the archives of the Brain Tumor Reference Center, Institute of Neuropathology, University of Bonn, Germany. DNA and RNA were extracted from FFPE tumor samples. Gene fusions were identified on the DNA level by FISH using break-apart probes for ALK, NTRK1, -2, -3, ROS1 and MET and Molecular Inversion Probe (MIP) methodology. For the detection of fusions on the RNA level, targeted RNA sequencing was performed as well as Nanostring-based detection with probes specific for recurrent fusions. 37 supratentorial GBM occurred in the first year of life, 13 GBM between one and four years. 18 cases showed fusions of ALK to different fusion partners; all occurred in the first year of life (18/37 cases, 48.6%). Fusions of ROS1 were found in 5, MET in 3, NTRK1, -2, -3 in 10 cases. 12 cases showed no and two novel fusions. The different methods led to comparable results. Only recurrent fusions with known fusion partners were detectable with probes designed for the fusion sequence, and library construction for targeted RNA sequencing was not successful in a fraction of cases. Break-apart FISH led to reliable results on the next day, and MIP technology represented the most sensitive method for analysis of FFPE samples. Gene fusions involving the tyrosine kinase genes ALK, MET, ROS1 and NTRK1, -2, -3 occurred in 72% of glioblastomas of children younger than four years; the most frequent were ALK fusions occurring in infant GBM. DNA based MIP technology represented the most robust and sensitive assay. Citation Format: Torsten Pietsch, Christian Vokuhl, Gerrit H. Gielen, Andre O. von Bueren, Evelyn Dörner, Glen Kristiansen, Andreas Waha, Christof Kramm. Frequent oncogenic tyrosine kinase gene fusions in supratentorial glioblastomas of young children [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-216.