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  CD74-NRG1 Fusions in Lung Adenocarcinoma

Fernandez-Cuesta, L., Plenker, D., Osada, H., Sun, R., Menon, R., Leenders, F., et al. (2014). CD74-NRG1 Fusions in Lung Adenocarcinoma. Cancer Discovery, 4(4), 415-422. doi:10.1158/2159-8290.CD-13-0633.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-1F8A-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-1F8B-4
Genre: Journal Article

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Fernandez-Cuesta, L., Author
Plenker, D., Author
Osada, H., Author
Sun, R.1, Author              
Menon, R., Author
Leenders, F., Author
Ortiz-Cuaran, S., Author
Peifer, M., Author
Bos, M., Author
Dassler, J., Author
Malchers, F., Author
Schöttle, J., Author
Vogel, W., Author
Dahmen, I., Author
Koker, M., Author
Ullrich, R. T., Author
Wright, G. M., Author
Russell, P. A., Author
Wainer, Z., Author
Solomon, B., Author
Brambilla, E., AuthorNagy-Mignotte, H., AuthorMoro-Sibilot, D., AuthorBrambilla, C. G., AuthorLantuejoul, S., AuthorAltmüller, J., AuthorBecker, C., AuthorNürnberg, P., AuthorHeuckmann, J. M., AuthorStoelben, E., AuthorPetersen, I., AuthorClement, J. H., AuthorSänger, J., AuthorMuscarella, L. A., Authorla Torre, A., AuthorFazio, V. M., AuthorLahortiga, I., AuthorPerera, T., AuthorOgata, S., AuthorParade, M., AuthorBrehmer, D., AuthorVingron, M.2, Author              Heukamp, L. C., AuthorBuettner, R., AuthorZander, T., AuthorWolf, J., AuthorPerner, S., AuthorAnsen, S., AuthorHaas, S. A.1, Author              Yatabe, Y., AuthorThomas, R. K., Author more..
Affiliations:
1Gene Structure and Array Design (Stefan Haas), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479640              
2Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              

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 Abstract: 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-beta3, 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.

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Language(s): eng - English
 Dates: 2014-01-272014-04
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1158/2159-8290.CD-13-0633
ISSN: 2159-8290 (Electronic)2159-8274 (Print)
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Title: Cancer Discovery
Source Genre: Journal
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Publ. Info: American Association for Cancer Research
Pages: - Volume / Issue: 4 (4) Sequence Number: - Start / End Page: 415 - 422 Identifier: -