دورية أكاديمية
CD74-NRG1 Fusions Are Oncogenic In Vivo and Induce Therapeutically Tractable ERBB2:ERBB3 Heterodimerization.
| العنوان: | CD74-NRG1 Fusions Are Oncogenic In Vivo and Induce Therapeutically Tractable ERBB2:ERBB3 Heterodimerization. |
|---|---|
| المؤلفون: | Werr L; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Plenker D; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany., Dammert MA; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany., Lorenz C; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany., Brägelmann J; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.; Mildred Scheel School of Oncology, Cologne, University Hospital Cologne, Medical Faculty, Cologne, Germany., Tumbrink HL; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany., Klein S; Institute of Pathology, Medical Faculty, University Hospital of Cologne, Cologne, Germany., Schmitt A; Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany., Büttner R; Institute of Pathology, Medical Faculty, University Hospital of Cologne, Cologne, Germany., Persigehl T; Department of Radiology, Medical Faculty and University Hospital Cologne, University of Cologne, Cologne, Germany., Shokat KM; Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California., Wunderlich FT; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.; Max Planck Institute for Metabolism Research, Cologne, Germany.; Institute for Genetics, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP) Cologne, Cologne, Germany., Schram AM; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell Medical College, New York, New York., Peifer M; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany., Sos ML; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany., Reinhardt HC; Department of Hematology and Stem Cell Transplantation, University Hospital Essen, University Duisburg-Essen, German Cancer Consortium (DKTK partner site Essen), Essen, Germany., Thomas RK; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Institute of Pathology, Medical Faculty, University Hospital of Cologne, Cologne, Germany.; DKFZ, German Cancer Research Center, German Cancer Consortium (DKTK), Heidelberg, Germany. |
| المصدر: | Molecular cancer therapeutics [Mol Cancer Ther] 2022 May 04; Vol. 21 (5), pp. 821-830. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research, Inc Country of Publication: United States NLM ID: 101132535 Publication Model: Print Cited Medium: Internet ISSN: 1538-8514 (Electronic) Linking ISSN: 15357163 NLM ISO Abbreviation: Mol Cancer Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Philadelphia, PA : American Association for Cancer Research, Inc., c2001- |
| مواضيع طبية MeSH: | Adenocarcinoma of Lung* , Lung Neoplasms*, Animals ; Carcinogenesis/genetics ; Humans ; Mice ; Neuregulin-1/genetics ; Oncogenes ; Receptor, ErbB-2/genetics ; Receptor, ErbB-3/genetics |
| مستخلص: | NRG1 fusions are recurrent somatic genome alterations occurring across several tumor types, including invasive mucinous lung adenocarcinomas and pancreatic ductal adenocarcinomas and are potentially actionable genetic alterations in these cancers. We initially discovered CD74-NRG1 as the first NRG1 fusion in lung adenocarcinomas, and many additional fusion partners have since been identified. Here, we present the first CD74-NRG1 transgenic mouse model and provide evidence that ubiquitous expression of the CD74-NRG1 fusion protein in vivo leads to tumor development at high frequency. Furthermore, we show that ERBB2:ERBB3 heterodimerization is a mechanistic event in transformation by CD74-NRG1 binding physically to ERBB3 and that CD74-NRG1-expressing cells proliferate independent of supplemented NRG1 ligand. Thus, NRG1 gene fusions are recurrent driver oncogenes that cause oncogene dependency. Consistent with these findings, patients with NRG1 fusion-positive cancers respond to therapy targeting the ERBB2:ERBB3 receptors. (©2022 The Authors; Published by the American Association for Cancer Research.) |
| References: | Nat Rev Neurosci. 2008 Jun;9(6):437-52. (PMID: 18478032) Cell Rep. 2017 Sep 19;20(12):2833-2845. (PMID: 28930680) Clin Cancer Res. 2019 Aug 15;25(16):4966-4972. (PMID: 30988082) Genes Chromosomes Cancer. 2021 Jul;60(7):474-481. (PMID: 33583086) Genesis. 2000 Nov-Dec;28(3-4):106-10. (PMID: 11105051) Genes Chromosomes Cancer. 2022 Mar;61(3):123-130. (PMID: 34747541) Bioinformatics. 2013 Jan 1;29(1):15-21. (PMID: 23104886) Cancer Discov. 2018 Jun;8(6):686-695. (PMID: 29610121) Cancer Discov. 2018 Sep;8(9):1087-1095. (PMID: 29802158) J Thorac Oncol. 2021 Jul;16(7):1149-1165. (PMID: 33839363) Ann Oncol. 2017 Dec 01;28(12):3092-3097. (PMID: 28950338) Cancer Discov. 2014 Apr;4(4):415-22. (PMID: 24469108) Clin Cancer Res. 2021 Jun 1;27(11):3154-3166. (PMID: 33824166) Genome Biol. 2014;15(12):550. (PMID: 25516281) Oncogene. 1997 Sep 18;15(12):1385-94. (PMID: 9333014) Nat Chem Biol. 2016 Nov;12(11):923-930. (PMID: 27595329) Nat Commun. 2021 Sep 17;12(1):5505. (PMID: 34535668) J Thorac Oncol. 2017 Aug;12(8):e107-e110. (PMID: 28502724) Clin Cancer Res. 2019 Aug 1;25(15):4674-4681. (PMID: 31068372) BMC Bioinformatics. 2011 Aug 04;12:323. (PMID: 21816040) Exp Cell Res. 2003 Mar 10;284(1):14-30. (PMID: 12648463) Cancer Res. 2016 Feb 15;76(4):974-83. (PMID: 26837769) Nature. 2012 Jul 26;487(7408):505-9. (PMID: 22763448) |
| معلومات مُعتمدة: | P30 CA008748 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (NRG1 protein, human) 0 (Neuregulin-1) 0 (Nrg1 protein, mouse) EC 2.7.10.1 (ERBB2 protein, human) EC 2.7.10.1 (ERBB3 protein, human) EC 2.7.10.1 (Receptor, ErbB-2) EC 2.7.10.1 (Receptor, ErbB-3) |
| تواريخ الأحداث: | Date Created: 20220305 Date Completed: 20220505 Latest Revision: 20240712 |
| رمز التحديث: | 20240712 |
| مُعرف محوري في PubMed: | PMC9377738 |
| DOI: | 10.1158/1535-7163.MCT-21-0820 |
| PMID: | 35247925 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-8514 |
|---|---|
| DOI: | 10.1158/1535-7163.MCT-21-0820 |