# NRG1 gene fusion

Source: https://onco.cc/biomarkers/nrg1-fusion/  
OnCo record `nrg1-fusion` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A rare fusion that joins the neuregulin 1 gene to a partner, leaving the HER3 ligand stuck on the cell surface where it switches HER3 on continuously. It is found in a small percentage of lung adenocarcinomas, particularly invasive mucinous adenocarcinoma in people who have never smoked, and in pancreatic and biliary cancers, and zenocutuzumab is approved for it.

## Summary

NRG1 encodes neuregulin 1, the ligand of HER3. A fusion (CD74::NRG1 and SLC3A2::NRG1 are the commonest partners) keeps the EGF-like domain of neuregulin tethered to the membrane, where it drives HER2-HER3 dimerisation and downstream signalling; the readout is filed under HER3 for that reason, and it is why a HER2 by HER3 bispecific antibody treats it. The fusions are rare, enriched in invasive mucinous adenocarcinoma of the lung and in people who have never smoked, and they are missed by DNA-only panels often enough that RNA sequencing is the recommended way to look for them. Zenocutuzumab (Bizengri) was approved by the FDA under accelerated approval on the basis of overall response rate and duration of response, for advanced unresectable or metastatic NRG1 fusion-positive non-small cell lung cancer and pancreatic adenocarcinoma after progression on prior systemic therapy, with cholangiocarcinoma added to the label in May 2026. No companion diagnostic is listed on the FDA device list for it; the label asks only that patients be selected on the presence of an NRG1 gene fusion in tumour specimens.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: NRG1 fusion; neuregulin 1 fusion; NRG1 gene rearrangement; CD74-NRG1; CD74::NRG1; SLC3A2-NRG1; NRG1-rearranged; NRG1+
- Tags: biomarker; fusion

## Notes

- Lung cancer: an NRG1 rearrangement is a ligand event rather than a kinase event. The fusion keeps the EGF-like domain of neuregulin 1 anchored at the cell surface, where it supplies the ligand for HER2 and HER3 dimers and switches on PI3K and AKT, which is why the treatment is an antibody aimed at the receptor pair and not a kinase inhibitor. It was found by transcriptome sequencing of 25 never-smoker lung adenocarcinomas and confirmed in 4 of 102 driver-negative tumours, every one of them the invasive mucinous subtype (Fernandez-Cuesta 2014). Across 21,858 tumours profiled by anchored multiplex RNA sequencing, 41 carried an NRG1 fusion, 0.2 percent; the 25 lung cases were the largest group and 0.3 percent of the lung cancers tested, with heterogeneous partner genes, so an assay that reports only named fusions misses most of them (Jonna 2019). cBioPortal structural variants record 7 of 2,422 in luad_mskcc_2023_met_organotropism and 2 of 232 never-smoker genomes.

## Sources

- BIZENGRI (zenocutuzumab) prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=203daea4-fc87-40a4-a92f-ba2351b16de1
- Jonna et al., Clin Cancer Res 2019: NRG1 fusions in 41 of 21,858 solid tumours profiled by RNA sequencing: https://doi.org/10.1158/1078-0432.CCR-19-0160
- Fernandez-Cuesta et al., Cancer Discov 2014: CD74-NRG1 fusions in invasive mucinous lung adenocarcinoma: https://doi.org/10.1158/2159-8290.CD-13-0633
- cBioPortal study luad_mskcc_2023_met_organotropism (MSK, Cancer Cell 2023; 2,653 MSK-IMPACT lung adenocarcinoma samples, 2,422 with copy number and structural variants): https://www.cbioportal.org/study/summary?id=luad_mskcc_2023_met_organotropism

## Connected records

- biomarkers: [HER2 (ERBB2) activating mutation](https://onco.cc/biomarkers/her2-mutation/), [NTRK1/2/3 gene fusion](https://onco.cc/biomarkers/ntrk-fusion/), [RET fusion and RET mutation](https://onco.cc/biomarkers/ret-fusion/), [ROS1 fusion (ROS1-positive)](https://onco.cc/biomarkers/ros1-fusion/)
- cancers: [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Invasive mucinous adenocarcinoma of the lung](https://onco.cc/cancers/invasive-mucinous-adenocarcinoma-lung/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/)
- targets: [HER2](https://onco.cc/targets/her2/), [HER3](https://onco.cc/targets/her3/), [NRG1](https://onco.cc/targets/nrg1/)
- drugs: [Zenocutuzumab](https://onco.cc/drugs/zenocutuzumab/)
- pathways: [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)
- terms: [Gene fusion](https://onco.cc/terms/gene-fusion/), [Lung cancer in never-smokers](https://onco.cc/terms/never-smoker-lung-cancer/), [Tumour-agnostic (tissue-agnostic) approval](https://onco.cc/terms/tumour-agnostic/)
- key papers: [CD74-NRG1 fusions in lung adenocarcinoma](https://onco.cc/key-papers/paper-fernandez-cuesta-cd74-nrg1-fusion-lung-cancer-discov-2014/), [Detection of NRG1 gene fusions in solid tumors](https://onco.cc/key-papers/paper-jonna-nrg1-fusions-solid-tumours-ccr-2019/)

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