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Clin Cancer Res. 2019 May 8. doi: 10.1158/1078-0432.CCR-19-0191. [Epub ahead of print]

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

Author information

1
BC Cancer, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada.
2
Pancreas Centre British Columbia, Vancouver, Canada.
3
BC Cancer, Division of Medical Oncology, Vancouver, British Columbia, Canada.
4
Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, British Columbia, Canada.
5
PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
6
Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
7
Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
8
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
9
Department of Molecular Biology and Biochemistry, Simon Fraser University, Vancouver, British Columbia, Canada.
10
Pancreas Centre British Columbia, Vancouver, Canada. drenouf@bccancer.bc.ca.

Abstract

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.

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