CD74-NRG1 Fusions in Lung Adenocarcinoma
| Autor: | Dirk Brehmer, Dennis Plenker, Benjamin Solomon, Stefan A. Haas, Mirjam Koker, Denis Moro-Sibilot, Zoe Wainer, Janine Altmüller, Hélène Nagy-Mignotte, Yasushi Yatabe, Gavin M. Wright, Prudence A. Russell, Thomas Zander, Roopika Menon, Annamaria la Torre, Timothy Perera, Sandra Ortiz-Cuaran, Marc Parade, Marc Bos, Elisabeth Brambilla, Erich Stoelben, Ruping Sun, Christian Becker, Vito Michele Fazio, Martin Vingron, Roman K. Thomas, Wenzel Vogel, Jakob Schöttle, Peter Nürnberg, Sylvie Lantuejoul, Idoya Lahortiga, Iver Petersen, Hirotaka Osada, Jürgen Wolf, Roland T. Ullrich, Souichi Ogata, Lucia Anna Muscarella, Jörg Sänger, Lukas C. Heukamp, Joachim H. Clement, Christian Brambilla, Johannes M. Heuckmann, Lynnette Fernandez-Cuesta, Sascha Ansén, Sven Perner, Reinhard Buettner, Martin Peifer, Frauke Leenders, Juliane Daßler, Ilona Dahmen, Florian Malchers |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Lung Neoplasms Oncogene Proteins Fusion Neuregulin-1 Molecular Sequence Data Adenocarcinoma of Lung Biology Adenocarcinoma Transcriptome Fusion gene Mice Cell Line Tumor mental disorders medicine ROS1 Animals Humans ERBB3 Aged Aged 80 and over Base Sequence Gene Expression Profiling Histocompatibility Antigens Class II Cancer Sequence Analysis DNA Middle Aged medicine.disease Adenocarcinoma Mucinous 3. Good health Gene expression profiling Antigens Differentiation B-Lymphocyte Oncology Immunology Cancer research NIH 3T3 Cells Ectopic expression Female Signal Transduction |
| Zdroj: | Cancer Discovery; Vol 4 Cancer Discovery |
| ISSN: | 2159-8274 |
| DOI: | 10.1158/2159-8290.CD-13-0633 |
| Popis: | 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. 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. Cancer Discov; 4(4); 415–22. ©2014 AACR. This article is highlighted in the In This Issue feature, p. 377 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|