Oncofusions form when chromosomal translocations join two genes to create a protein with oncogenic properties. The oncogenic ETV6-NTRK3 (EN) gene fusion joins the sterile alpha domain of the ETV6 transcription factor with the tyrosine kinase domain of the neurotrophin-3 receptor NTRK3. Four EN variants with alternating break points have since been detected in a wide range of human cancers. To provide insight into EN oncogenesis, we employed a proximity labeling mass spectrometry approach to define the molecular context of the fusions. We identify 237 high-confidence interactors, which link EN fusions to several key signaling pathways, including ERBB, Insulin and JAK/STAT. We then assess the effects of EN variants on these pathways, and show that the pan NTRK inhibitor selitrectinib (LOXO-195) inhibits the oncogenic activity of EN2, the most common variant. This systems-level analysis of defines the molecular framework in which EN oncofusions operate to promote cancer.
[doi:10.25345/C5BK1702Q]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Protein protein interactions ; Oncogenic ; Fusion
Principal Investigators: (in alphabetical order) |
Markku Varjosalo, University of Helsinki, Finland |
Submitting User: | XIOLIU |
Number of Files: | |
Total Size: | |
Spectra: | |
Subscribers: | |
Owner | Reanalyses | |
---|---|---|
Experimental Design | ||
Conditions:
|
||
Biological Replicates:
|
||
Technical Replicates:
|
||
Identification Results | ||
Proteins (Human, Remapped):
|
||
Proteins (Reported):
|
||
Peptides:
|
||
Variant Peptides:
|
||
PSMs:
|
||
Quantification Results | ||
Differential Proteins:
|
||
Quantified Proteins:
|
||
Browse Dataset Files | |
FTP Download Link (click to copy):
|