NRG1 Gene Fusions Are Recurrent, Clinically Actionable Gene Rearrangements in KRAS Wild-Type Pancreatic Ductal Adenocarcinoma

Clin Cancer Res. 2019 Aug 1;25(15):4674-4681. doi: 10.1158/1078-0432.CCR-19-0191. Epub 2019 May 8.


Purpose: Gene fusions involving neuregulin 1 (NRG1) have been noted in multiple cancer types and have potential therapeutic implications. Although varying results have been reported in other cancer types, the efficacy of the HER-family kinase inhibitor afatinib in the treatment of NRG1 fusion-positive pancreatic ductal adenocarcinoma is not fully understood.

Experimental design: Forty-seven patients with pancreatic ductal adenocarcinoma received comprehensive whole-genome and transcriptome sequencing and analysis. Two patients with gene fusions involving NRG1 received afatinib treatment, with response measured by pretreatment and posttreatment PET/CT imaging.

Results: Three of 47 (6%) patients with advanced pancreatic ductal adenocarcinoma were identified as KRAS wild type by whole-genome sequencing. All KRAS wild-type tumors were positive for gene fusions involving the ERBB3 ligand NRG1. Two of 3 patients with NRG1 fusion-positive tumors were treated with afatinib and demonstrated a significant and rapid response while on therapy.

Conclusions: This work adds to a growing body of evidence that NRG1 gene fusions are recurrent, therapeutically actionable genomic events in pancreatic cancers. Based on the clinical outcomes described here, patients with KRAS wild-type tumors harboring NRG1 gene fusions may benefit from treatment with afatinib.See related commentary by Aguirre, p. 4589.

MeSH terms

  • Female
  • Gene Fusion
  • Gene Rearrangement
  • Humans
  • Lung Neoplasms / genetics*
  • Neuregulin-1
  • Oncogene Proteins, Fusion / genetics
  • Pancreatic Neoplasms*
  • Positron Emission Tomography Computed Tomography
  • Proto-Oncogene Proteins p21(ras)


  • KRAS protein, human
  • NRG1 protein, human
  • Neuregulin-1
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins p21(ras)