Pattwell, Siobhan SArora, SonaliCimino, Patrick JOzawa, TatsuyaSzulzewsky, FrankHoellerbauer, PiaBonifert, TobiasHoffstrom, Benjamin GBoiani, Norman EBolouri, HamidCorrenti, Colin EOldrini, BarbaraSilber, John RPaddison, Patrick JHolland, Eric CSquatrito, Massimo2021-03-092021-03-092020-11-01Nat Commun.2020;11(1):2977http://hdl.handle.net/20.500.12105/12179Independent scientific achievements have led to the discovery of aberrant splicing patterns in oncogenesis, while more recent advances have uncovered novel gene fusions involving neurotrophic tyrosine receptor kinases (NTRKs) in gliomas. The exploration of NTRK splice variants in normal and neoplastic brain provides an intersection of these two rapidly evolving fields. Tropomyosin receptor kinase B (TrkB), encoded NTRK2, is known for critical roles in neuronal survival, differentiation, molecular properties associated with memory, and exhibits intricate splicing patterns and post-translational modifications. Here, we show a role for a truncated NTRK2 splice variant, TrkB.T1, in human glioma. TrkB.T1 enhances PDGF-driven gliomas in vivo, augments PDGF-induced Akt and STAT3 signaling in vitro, while next generation sequencing broadly implicates TrkB.T1 in the PI3K signaling cascades in a ligand-independent fashion. These TrkB.T1 findings highlight the importance of expanding upon whole gene and gene fusion analyses to include splice variants in basic and translational neuro-oncology research.engVoRRNA SplicingAnimalsBrainBrain NeoplasmsCarcinogenesisCells, CulturedGene Expression ProfilingGene OntologyGliomaHigh-Throughput Nucleotide SequencingHumansMembrane GlycoproteinsMiceNIH 3T3 CellsNeural Stem CellsOncogene Proteins, FusionOncogenesPhosphatidylinositol 3-KinasesRNA IsoformsReceptor, trkBSignal TransductionAtribución-NoComercial-CompartirIgual 4.0 Internacional32532995111297710.1038/s41467-020-16786-52041-1723Nature communicationsopen access