Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development.

Cancer Cell 2018 07;34(1):163-177.e7

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; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

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 (EGFR). Quantitative multi-parametric magnetic resonance imaging analyses indicated increased tumor invasion for EGFR mutants, corroborated in mice bearing intracranial tumors expressing EGFR and dependent on ERK-mediated expression of matrix metalloproteinase-1. EGFR 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 EGFR mutation in glioblastoma, postulating EGFR as a molecular marker for responsiveness to therapy with EGFR-targeting antibodies.

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http://dx.doi.org/10.1016/j.ccell.2018.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424337PMC
July 2018
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