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Reading the active genes of 25 lung cancers from people who had never smoked turned up a fusion that does something unusual: instead of switching on a receptor directly, it hangs the receptor's own trigger on the outside of the cell.
A novel somatic gene fusion, CD74-NRG1, was discovered by transcriptome sequencing of 25 lung adenocarcinomas from never smokers. Screening 102 lung adenocarcinomas negative for known oncogenic alterations found four additional fusion-positive tumours, all of the invasive mucinous subtype. Mechanistically, CD74-NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-beta3, providing the ligand for ERBB2-ERBB3 receptor complexes. ERBB2 and ERBB3 expression was high in the index case, phospho-ERBB3 expression was specific to fusion-positive tumours, and ectopic expression of the fusion in lung cancer cells expressing both receptors activated ERBB3 and the PI3K-AKT pathway and increased colony formation in soft agar.
It identified a driver in the one lung histology that had none, and it defined a mechanism, ligand presentation, that requires an antibody against the receptor pair rather than a kinase inhibitor.
Shares NRG1 gene fusion, NRG1, Gene fusion, Receptor tyrosine kinase activation.
Shares NRG1 gene fusion, NRG1, Non-small-cell lung cancer.
Shares NRG1, Cancer Discovery, Receptor tyrosine kinase activation, RNA sequencing & expression profiling.
Shares NRG1 gene fusion, NRG1, Receptor tyrosine kinase activation, HER2.
Shares Roman Thomas, Receptor tyrosine kinase activation, Non-small-cell lung cancer.
Shares Cancer Discovery, Driver mutation, Receptor tyrosine kinase activation, HER2.
Shares Gene fusion, Receptor tyrosine kinase activation, RNA sequencing & expression profiling, HER2.
Shares Gene fusion, Driver mutation, Receptor tyrosine kinase activation, Non-small-cell lung cancer.