Journal article

CD74-NRG1 Fusions in Lung Adenocarcinoma

Lynnette Fernandez-Cuesta, Dennis Plenker, Hirotaka Osada, Ruping Sun, Roopika Menon, Frauke Leenders, Sandra Ortiz-Cuaran, Martin Peifer, Marc Bos, Juliane Dassler, Florian Malchers, Jakob Schottle, Wenzel Vogel, Ilona Dahmen, Mirjam Koker, Roland T Ullrich, Gavin M Wright, Prudence A Russell, Zoe Wainer, Benjamin Solomon Show all

CANCER DISCOVERY | AMER ASSOC CANCER RESEARCH | Published : 2014

Abstract

UNLABELLED: We discovered a novel somatic gene fusion, CD74-NRG1, by transcriptome sequencing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocarcinomas negative for known oncogenic alterations, we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74-NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-β3, thereby providing the ligand for ERBB2-ERBB3 receptor complexes. Accordingly, ERBB2 and ERBB3 expression was high in the index case, and expression of phospho-ERBB3 was specifically found in tumors bearing the fusion (P < 0.0001). Ectopic expression of CD74-NRG1 in lung cancer ce..

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Grants

Awarded by Deutsche Krebshilfe as part of the small-cell lung cancer genome-sequencing consortium


Awarded by EU-Framework Programme CURELUNG


Awarded by Deutsche Forschungsgemeinschaft


Awarded by German Ministry of Science and Education (BMBF) as part of the NGFNplus program


Awarded by Stand Up To Cancer Innovative Research Grant, a Program of the Entertainment Industry Foundation


Awarded by Italian Ministry of Health


Awarded by GR Program


Awarded by IWT


Awarded by Grants-in-Aid for Scientific Research


Funding Acknowledgements

This work was supported by the Deutsche Krebshilfe as part of the small-cell lung cancer genome-sequencing consortium (grant ID: 109679 to R. K. Thomas, M. Peifer, R. Buettner, S. A. Haas, and M. Vingron); by the EU-Framework Programme CURELUNG (HEALTH-F2-2010-258677 to E. Brambilla, J. Wolf, and R. K. Thomas); by the Deutsche Forschungsgemeinschaft through TH1386/3-1 (to R. K. Thomas); and through SFB832 (TP5 to L. C. Heukamp; and TP6 to R. T. Ullrich, J. Wolf, and R. K. Thomas); by the German Ministry of Science and Education (BMBF) as part of the NGFNplus program (grant 01GS08101 to J. Wolf and R. K. Thomas); by the Deutsche Krebshilfe as part of the Oncology Centers of Excellence funding program (to R. Buettner, J. Wolf, and R. K. Thomas); by a Stand Up To Cancer Innovative Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-IRG60109 to R. K. Thomas); by funds of the DFG Excellence Cluster ImmunoSensation (to J. Dassler); by the Italian Ministry of Health (Ricerca Corrente RC1303LO57 and GR Program 2010-2316264) and by the "5 x 1000" voluntary contributions (to L. A. Muscarella); by the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), Ministry of Education, Culture, Sports, Science and Technology of Japan (to Y. Yatabe); by a research project grant (IWT 110431 to D. Brehmer); by the Belgium government agency for Innovation by Science and Technology (IWT; to I. Lahortiga, S. Ogata, M. Parade, T. Perera, and D. Brehmer); and by Agiradom and French Health Ministry (PPHRC; to C. G. Brambilla).