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NRG1 fusions in KRAS wild-type pancreatic cancer

We used whole-genome and transcriptome sequencing to identify clinically actionable genomic alterations in young adults with pancreatic ductal adenocarcinoma (PDAC). Molecular characterization of 17 PDAC patients enrolled in a precision oncology program revealed gene fusions amenable to pharmacologi...

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Main Authors: Heining, Christoph (Author) , Horak, Peter (Author) , Richter, Daniela (Author) , Penzel, Roland (Author) , Endris, Volker (Author) , Ehrenberg, Karl Roland (Author) , Frank, Stephanie (Author) , Giese, Nathalia (Author) , Strobel, Oliver (Author) , Hackert, Thilo (Author) , Springfeld, Christoph (Author) , Bergmann, Frank (Author) , Kalle, Christof von (Author) , Scholl, Claudia (Author) , Ball, Claudia R. (Author) , Stenzinger, Albrecht (Author) , Fröhling, Stefan (Author) , Glimm, Hanno (Author)
Format: Article (Journal)
Language:English
Published: May 25, 2018
In: Cancer discovery
Year: 2018, Volume: 8, Issue: 9, Pages: 1087-1095
ISSN:2159-8290
DOI:10.1158/2159-8290.CD-18-0036
Online Access:Verlag, Volltext: http://dx.doi.org/10.1158/2159-8290.CD-18-0036
Verlag, Volltext: http://cancerdiscovery.aacrjournals.org/content/early/2018/05/25/2159-8290.CD-18-0036
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Author Notes:Christoph Heining, Peter Horak, Sebastian Uhrig, Paula L. Codo, Barbara Klink, Barbara Hutter, Martina Fröhlich, David Bonekamp, Daniela Richter, Katja Steiger, Roland Penzel, Volker Endris, Karl Roland Ehrenberg, Stephanie Frank, Kortine Kleinheinz, Umut H. Toprak, Matthias Schlesner, Ranadip Mandal, Lothar Schulz, Helmut Lambertz, Sebastian Fetscher, Michael Bitzer, Nisar P. Malek, Marius S. Horger, Nathalia A. Giese, Oliver Strobel, Thilo Hackert, Christoph Springfeld, Lars Feuerbach, Frank Bergmann, Evelin Schröck, Christof von Kalle, Wilko Weichert, Claudia Scholl, Claudia R. Ball, Albrecht Stenzinger, Benedikt Brors, Stefan Fröhling, Hanno Glimm
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Summary:We used whole-genome and transcriptome sequencing to identify clinically actionable genomic alterations in young adults with pancreatic ductal adenocarcinoma (PDAC). Molecular characterization of 17 PDAC patients enrolled in a precision oncology program revealed gene fusions amenable to pharmacologic inhibition by small-molecule tyrosine kinase inhibitors in all patients with KRAS wild-type (KRASwt) tumors (4 of 17). These alterations included recurrent NRG1 rearrangements predicted to drive PDAC development through aberrant ERBB receptor-mediated signaling, and pharmacologic ERBB inhibition resulted in clinical improvement and remission of liver metastases in two patients with NRG1-rearranged tumors that had proved resistant to standard treatment. Our findings demonstrate that systematic screening of KRASwt tumors for oncogenic fusion genes will substantially improve the therapeutic prospects for a sizeable fraction of PDAC patients.
Item Description:Published onlinefirst May 25, 2018
Gesehen am 17.07.2018
Physical Description:Online Resource
ISSN:2159-8290
DOI:10.1158/2159-8290.CD-18-0036

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