P16.10.A UNRAVELING THE CLINICAL IMPLICATIONS OF TRIM24::NTRK2 FUSION GENE IN PEDIATRIC HIGH-GRADE GLIOMA: A CASE STUDY

Abstract

Abstract BACKGROUND High-grade gliomas are among the deadliest of all childhood cancers and the leading cause of cancer-related mortality in children. The standard treatment is resection followed by chemotherapy, most often temozolomide and radiation therapy. Unfortunately, there is no evidence that temozolomide influences survival in pediatric patients and only a limited number of new drugs have been identified for specific subgroups of tumors. The identification of fusion genes as possible drivers of the disease offers an opportunity for targeted therapies. We present a case of a six-year-old patient with a novel TRIM24::NTRK2 fusion positive epithelioid glioblastoma with subsequent relapses. METHODS We investigated the ramification of this fusion and evolution of the tumor through whole genome sequencing, RNA-sequencing and DNA methylation profiling, and studied the effect of the patient’s treatment using patient-derived cell cultures. RESULTS Our studies show that the TRIM24::NTRK2 fusion has oncogenic abilities but loses its importance as the tumor evolves. In addition, we demonstrate an increased drug resistance over time, further indicating the diminished driver function of the fusion. CONCLUSION The use of resequencing revealed parallel development of tumor subclones with different genomic alterations, highlighting the importance of genomic profiling from various parts of the tumor. FUNDING This work was supported by the Swedish Research Council, the Swedish Childhood Cancer Foundation, and the Swedish Cancer Society