{"entity":{"id":"paper-fernandez-cuesta-cd74-nrg1-fusion-lung-cancer-discov-2014","kind":"paper","name":"CD74-NRG1 fusions in lung adenocarcinoma","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-25","links":[{"label":"Fernandez-Cuesta et al., Cancer Discov 2014: CD74-NRG1 fusions in invasive mucinous lung adenocarcinoma","url":"https://doi.org/10.1158/2159-8290.CD-13-0633"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24469108/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["rna-seq"],"targets":["nrg1","her2"],"drugs":[],"companies":[],"institutions":[],"pathways":["rtk-activation","pi3k-akt-mtor"],"terms":["gene-fusion","driver-mutation"],"trials":[],"people":["roman-thomas"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2014,"doi":"10.1158/2159-8290.CD-13-0633","pmid":"24469108","authors":"Fernandez-Cuesta L, Plenker D, Osada H, et al.","paperType":"basic","findings":["CD74-NRG1 fusions discovered in never-smoker lung adenocarcinoma.","All additional cases were of the invasive mucinous subtype, a histology with no effective treatment.","The fusion supplies a ligand for HER2-HER3 dimers rather than activating a kinase directly.","Fusion-positive tumours show specific phospho-ERBB3 expression."],"whatItMeans":"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.","caveats":["Very small numbers: one index case and four confirmations.","Requires RNA sequencing to detect, so prevalence from DNA panels is an undercount.","No approved therapy in this class at the time of publication."],"changedPractice":false},"route":"/key-papers/paper-fernandez-cuesta-cd74-nrg1-fusion-lung-cancer-discov-2014/","neighbours":{"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"nrg1","kind":"target","name":"NRG1","route":"/targets/nrg1/"}],"pathway":[{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"term":[{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"}],"person":[{"id":"roman-thomas","kind":"person","name":"Roman Thomas","route":"/people/roman-thomas/"}],"journal":[{"id":"cancer-discovery","kind":"journal","name":"Cancer Discovery","route":"/journals/cancer-discovery/"}],"biomarker":[{"id":"nrg1-fusion","kind":"biomarker","name":"NRG1 gene fusion","route":"/biomarkers/nrg1-fusion/"}]}}