A kinase-deficient NTRK2 splice variant predominates in glioma and amplifies several oncogenic signaling pathways.

Nature Communications
Siobhan S PattwellEric C Holland

Abstract

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.

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Citations

Nov 13, 2021·Current Opinion in Neurology·Peter L Kim

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Datasets Mentioned

BETA
GSE150653

Methods Mentioned

BETA
GTPases
RNASeq
PCA
protein assay
reverse transcription PCR
PCR
flow cytometry
electrophoresis
Assay
mechanical dissociations

Software Mentioned

R
nextpresso
ImageJ
R Bioconductor Packages clusterProfiler
R Bioconductor package DOSE
DGCA
eSlideManager
Bowtie
DESeq2
Cufflinks

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