2026-06-14T16:49:10Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/121792024-11-29T19:26:08Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
United States Department of Health and Human Services
funder
American Cancer Society
funder
French Development Agency
funder
Alzheimer's Disease Research Center
2021-03-09T15:47:29Z
2021-03-09T15:47:29Z
2020-11-01
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
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.
eng
A kinase-deficient NTRK2 splice variant predominates in glioma and amplifies several oncogenic signaling pathways.
journal article
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