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| Status |
Public on May 13, 2020 |
| Title |
NTRK2 splice variant, TrkB.T1, is the predominant isoform in gliomas and enhances gliomagenesis via PI3K signaling |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Independent scientific achievements have led to the discovery of aberrant splicing patterns in oncogenesis while more recent advances have uncovered novel gene fusions involving NTRK2 in gliomas. The exploration of NTRK2 splice variants in normal and neoplastic brain provides an intersection of these two rapidly evolving fields – alternative splicing and NTRK2 involvement in brain tumors. Tropomyosin receptor B (TrkB), encoded by the NTRK2 gene, is known for critical roles in neuronal survival, differentiation, molecular properties associated with memory, and exhibits intricate splicing patterns. Here we show a novel role for a TrkB splice variant, TrkB.T1, in human glioma via NTRK2 transcript analyses and immunostaining using a novel antibody. TrkB.T1 enhances PDGF-driven gliomas in vivo, augments PDGF-induced Akt signaling in vitro, while next generation sequencing broadly implicates TrkB.T1 in the PI3K/Akt signaling cascade in a ligand independent fashion. NTRK2 appears to be a specific example that highlights the importance of expanding upon whole gene and gene fusion analyses to explore splice variants in basic and translational neuro-oncology research
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| Overall design |
For infection of NSC-U5 cells, 1e5 cells/well were seeded into 6-well plates. Lentivirus was used unconcentrated and cells were infected at a MOI<1 24 hours after seeding. 72 hours after seeding, selection was begun for cells successfully expressing the constructs using 2 μg/mL puromycin (for 3 days). Cells were expanded after selection to create a stable line and collected for RNAseq three weeks post infection.
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| Contributor(s) |
Pattwell SS, Arora S, Cimino PJ, Ozawa T, Szulzewsky F, Hoellerbauer P, Hoffstrom BG, Boiani NE, Bolouri H, Correnti CE, Silber JR, Paddison P, Holland EC |
| Citation(s) |
32532995 |
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| Submission date |
Sep 04, 2019 |
| Last update date |
Jun 22, 2020 |
| Contact name |
Sonali Arora |
| E-mail(s) |
sarora@fredhutch.org
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| Organization name |
FHCRC
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| Street address |
1100 Fairview Ave N,
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA563892 |
| SRA |
SRP220346 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE136868_RAW.tar |
950.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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