Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development Academic Article uri icon

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.

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 JD
  • Nasrallah, MacLean P
  • Ma, Jianhui
  • Zanca, Ciro
  • Scott, Andrew M
  • Orellana, Laura
  • Davatzikos, Christos
  • Furnari, Frank B
  • O'Rourke, Donald M

publication date

  • 2018

has subject area