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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, RNA sequencing & expression profiling.
Shares NRG1 gene fusion, NRG1, Non-small-cell lung cancer.
Shares NRG1, Cancer Discovery, RNA sequencing & expression profiling, Receptor tyrosine kinase activation.
Shares NRG1 gene fusion, NRG1, Receptor tyrosine kinase activation, HER2.
Shares Cancer Discovery, Driver mutation, Receptor tyrosine kinase activation, HER2.
Shares Roman Thomas, Receptor tyrosine kinase activation, Non-small-cell lung cancer.
Shares Gene fusion, RNA sequencing & expression profiling, Receptor tyrosine kinase activation, HER2.
Shares Gene fusion, Driver mutation, Receptor tyrosine kinase activation, Non-small-cell lung cancer.