Journal Article

DKFZ-2018-01482

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png NRG1 Fusions in KRAS Wild-Type Pancreatic Cancer.

Heining, C. (First author)DKFZ* ; Horak, P.DKFZ* ; Uhrig, S. (First author)DKFZ* ; Codo, P. L.DKFZ* ; Klink, B.DKFZ* ; Hutter, B.DKFZ* ; Fröhlich, M. A.DKFZ* ; Bonekamp, D.DKFZ* ; Richter, D.DKFZ* ; Steiger, K.DKFZ* ; Penzel, R. ; Endris, V. ; Ehrenberg, K. R.DKFZ* ; Frank, S.DKFZ* ; Kleinheinz, K.DKFZ* ; Toprak, U.DKFZ* ; Schlesner, M.DKFZ* ; Mandal, R.DKFZ* ; Schulz, L. ; Lambertz, H. ; Fetscher, S. ; Bitzer, M. ; Malek, N. P. ; Horger, M. ; Giese, N. A. ; Strobel, O. ; Hackert, T. ; Springfeld, C. ; Feuerbach, L.DKFZ* ; Bergmann, F. ; Schröck, E.DKFZ* ; von Kalle, C.DKFZ* ; Weichert, W.DKFZ* ; Scholl, C.DKFZ* ; Ball, C.DKFZ* ; Stenzinger, A.DKFZ* ; Brors, B.DKFZ* ; Fröhling, S. (Last author)DKFZ* ; Glimm, H.DKFZ*

2018
Philadelphia, Pa.

This record in other databases:  

Please use a persistent id in citations: doi:10.1158/2159-8290.CD-18-0036

Abstract: 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 patients with PDAC 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 2 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 patients with PDAC.Significance: Advanced PDAC is a malignancy with few treatment options that lacks molecular mechanism-based therapies. Our study uncovers recurrent gene rearrangements such as NRG1 fusions as disease-driving events in KRASwt tumors, thereby providing novel insights into oncogenic signaling and new therapeutic options in this entity. Cancer Discov; 8(9); 1087-95. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 1047.

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Contributing Institute(s):

1. NCT DD Translationale Medizinische Onkologie (G911)
2. DKTK Dresden (L301)
3. DKTK Heidelberg (L101)
4. Angewandte Bioinformatik (G200)
5. E010 Radiologie (E010)
6. DKTK München (L701)
7. Theoretische Bioinformatik (B080)
8. Bioinformatik und Omics Data Analytics (B240)
9. DKTK Tübingen (L801)
10. Translationale Onkologie (G100)
11. Angewandte Funktionelle Genomik (B290)

Research Program(s):

1. 317 - Translational cancer research (POF3-317) (POF3-317)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; IF >= 15 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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