Abstract
The RET kinase receptor is a target of mutations in neural crest tumors, including pheochromocytomas, and of oncogenic fusions in epithelial cancers. We report a RET::GRB2 fusion in a pheochromocytoma in which RET, functioning as the upstream partner, retains its kinase domain but loses critical C-terminal motifs and is fused to GRB2, a physiological RET interacting protein. RET::GRB2 is an oncogenic driver that leads to constitutive, ligand-independent RET signaling; has transforming capability dependent on RET catalytic function; and is sensitive to RET inhibitors. These observations highlight a new driver event in pheochromocytomas potentially amenable for RET-driven therapy.
Original language | English (US) |
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Article number | 100686 |
Journal | Cell Reports Medicine |
Volume | 3 |
Issue number | 7 |
DOIs | |
State | Published - Jul 19 2022 |
Keywords
- GRB2
- RET fusion
- RET mutation
- driver genetic events
- oncogenic fusion
- paraganglioma
- pheochromocytoma
- pralsetinib
- selpercatinib
- tyrosine kinase inhibitor
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology