L. Wang, A. Yekula, K. Muralidharan, J. L. Small, Z. S. Rosh, K. M. Kang, B. S. Carter, and L. Balaj. Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma. Cancers (Basel), May 2020. [PubMed Central:\href https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281415PMC7281415] [DOI:\href https://dx.doi.org/10.3390/cancers1205121910.3390/cancers12051219] [PubMed:\href https://www.ncbi.nlm.nih.gov/pubmed/2845378428453784].


Sequencing studies have provided novel insights into the heterogeneous molecular landscape of glioblastoma (GBM), unveiling a subset of patients with gene fusions. Tissue biopsy is highly invasive, limited by sampling frequency and incompletely representative of intra-tumor heterogeneity. Extracellular vesicle-based liquid biopsy provides a minimally invasive alternative to diagnose and monitor tumor-specific molecular aberrations in patient biofluids. Here, we used targeted RNA sequencing to screen GBM tissue and the matched plasma of patients (n = 9) for RNA fusion transcripts. We identified two novel fusion transcripts in GBM tissue and five novel fusions in the matched plasma of GBM patients. The fusion transcripts FGFR3-TACC3 and VTI1A-TCF7L2 were detected in both tissue and matched plasma. A longitudinal follow-up of a GBM patient with a FGFR3-TACC3 positive glioma revealed the potential of monitoring RNA fusions in plasma. In summary, we report a sensitive RNA-seq-based liquid biopsy strategy to detect RNA level fusion status in the plasma of GBM patients.