2026-06-14T16:49:10Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/121792024-11-29T19:26:08Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Pattwell, Siobhan S author Arora, Sonali author Cimino, Patrick J author Ozawa, Tatsuya author Szulzewsky, Frank author Hoellerbauer, Pia author Bonifert, Tobias author Hoffstrom, Benjamin G author Boiani, Norman E author Bolouri, Hamid author Correnti, Colin E author Oldrini, Barbara author Silber, John R author Paddison, Patrick J author Holland, Eric C author Squatrito, Massimo author 2020-11-01 Independent 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. Nat Commun.2020;11(1):2977 10.1038/s41467-020-16786-5 2041-1723 Nature communications 32532995 http://hdl.handle.net/20.500.12105/12179 A kinase-deficient NTRK2 splice variant predominates in glioma and amplifies several oncogenic signaling pathways.