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https://ahro.austin.org.au/austinjspui/handle/1/18246| Title: | Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development. | Austin Authors: | Binder, Zev A;Thorne, Amy Haseley;Bakas, Spyridon;Wileyto, E Paul;Bilello, Michel;Akbari, Hamed;Rathore, Saima;Ha, Sung Min;Zhang, Logan;Ferguson, Cole J;Dahiya, Sonika;Bi, Wenya Linda;Reardon, David A;Idbaih, Ahmed;Felsberg, Joerg;Hentschel, Bettina;Weller, Michael;Bagley, Stephen J;Morrissette, Jennifer J D;Nasrallah, MacLean P;Ma, Jianhui;Zanca, Ciro;Scott, Andrew M ;Orellana, Laura;Davatzikos, Christos;Furnari, Frank B;O'Rourke, Donald M | Affiliation: | Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Ludwig Institute for Cancer Research, La Jolla, San Diego 92093, USA Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63108, USA Center for Skull Base and Pituitary Surgery, Department of Neurosurgery, Brigham and Woman's Hospital, Harvard Medical Center, Boston, MA 02115, USA Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, AP-HP, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris 75013, France Institute of Neuropathology, Heinrich Heine University, Medical Faculty, Moorenstrasse 5, Duesseldorf 40225, Germany Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Medical Faculty, Härtelstrasse 16, Leipzig 04107, Germany Department of Neurology, University Hospital and University of Zurich, Zurich 8091, Switzerland Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Division of Neuropathology, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia |
Issue Date: | 9-Jul-2018 | Publication information: | Cancer cell 2018; 34(1): 163-177.e7 | Abstract: | We explored the clinical and pathological impact of epidermal growth factor receptor (EGFR) extracellular domain missense mutations. Retrospective assessment of 260 de novo glioblastoma patients revealed a significant reduction in overall survival of patients having tumors with EGFR mutations at alanine 289 (EGFRA289D/T/V). Quantitative multi-parametric magnetic resonance imaging analyses indicated increased tumor invasion for EGFRA289D/T/V mutants, corroborated in mice bearing intracranial tumors expressing EGFRA289V and dependent on ERK-mediated expression of matrix metalloproteinase-1. EGFRA289V tumor growth was attenuated with an antibody against a cryptic epitope, based on in silico simulation. The findings of this study indicate a highly invasive phenotype associated with the EGFRA289V mutation in glioblastoma, postulating EGFRA289V as a molecular marker for responsiveness to therapy with EGFR-targeting antibodies. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/18246 | DOI: | 10.1016/j.ccell.2018.06.006 | ORCID: | 0000-0002-6656-295X | Journal: | Cancer cell | PubMed URL: | 29990498 | Type: | Journal Article | Subjects: | A289D/T/V EGFR EGFR oncogenes EGFR targeted therapy GBM glioblastoma glioma radiogenomics radiomics survival |
| Appears in Collections: | Journal articles |
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