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. 2014 Apr;4(4):415-22.
doi: 10.1158/2159-8290.CD-13-0633. Epub 2014 Jan 27.

CD74-NRG1 fusions in lung adenocarcinoma

Lynnette Fernandez-Cuesta  1 , Dennis Plenker, Hirotaka Osada, Ruping Sun, Roopika Menon, Frauke Leenders, Sandra Ortiz-Cuaran, Martin Peifer, Marc Bos, Juliane Daßler, Florian Malchers, Jakob Schöttle, Wenzel Vogel, Ilona Dahmen, Mirjam Koker, Roland T Ullrich, Gavin M Wright, Prudence A Russell, Zoe Wainer, Benjamin Solomon, Elisabeth Brambilla, Hélène Nagy-Mignotte, Denis Moro-Sibilot, Christian G Brambilla, Sylvie Lantuejoul, Janine Altmüller, Christian Becker, Peter Nürnberg, Johannes M Heuckmann, Erich Stoelben, Iver Petersen, Joachim H Clement, Jörg Sänger, Lucia A Muscarella, Annamaria la Torre, Vito M Fazio, Idoya Lahortiga, Timothy Perera, Souichi Ogata, Marc Parade, Dirk Brehmer, Martin Vingron, Lukas C Heukamp, Reinhard Buettner, Thomas Zander, Jürgen Wolf, Sven Perner, Sascha Ansén, Stefan A Haas, Yasushi Yatabe, Roman K Thomas
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CD74-NRG1 fusions in lung adenocarcinoma

Lynnette Fernandez-Cuesta et al. Cancer Discov. 2014 Apr.

Abstract (V体育平台登录)

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 cell lines expressing ERBB2 and ERBB3 activated ERBB3 and the PI3K-AKT pathway, and led to increased colony formation in soft agar VSports手机版. Thus, CD74-NRG1 gene fusions are activating genomic alterations in invasive mucinous adenocarcinomas and may offer a therapeutic opportunity for a lung tumor subtype with, so far, no effective treatment. .

Significance: CD74–NRG1 fusions may represent a therapeutic opportunity for invasive mucinous lung adenocarcinomas, a tumor with no effective treatment that frequently presents with multifocal unresectable disease. V体育安卓版.

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