NRG1 Gene Fusions Are Recurrent, Clinically Actionable Gene Rearrangements in KRAS Wild-Type Pancreatic Ductal Adenocarcinoma
| Autor: | Janessa Laskin, Sharlene Gill, Jennifer J. Knox, David F. Schaeffer, Martin R. Jones, Marco A. Marra, Howard John Lim, Daniel J. Renouf, James T. Topham, Steven Gallinger, Hui-Li Wong, Karen Mungall, Julie Ho, Richard A. Moore, Angela Goytain, Malcolm J. Moore, Steven J.M. Jones, Yussanne Ma, Andrew J. Mungall, Laura Williamson, Wei Zhang, Robert E. Denroche, Yaoquing Shen, Michael K.C. Lee, Erin Pleasance, Sara Sadeghi, Gun-Ho Jang, Stephen Yip, Joanna M. Karasinska, Carolyn Reisle, Tony Ng, John Paul McGhie |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research biology business.industry Afatinib Wild type Cancer Gene rearrangement medicine.disease medicine.disease_cause Fusion gene 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology 030220 oncology & carcinogenesis mental disorders biology.protein medicine Cancer research ERBB3 KRAS Neuregulin 1 business medicine.drug |
| Zdroj: | Clinical Cancer Research. 25:4674-4681 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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