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

2018-07-09

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

A289D/T/V

EGFR

EGFR oncogenes

EGFR targeted therapy

GBM

glioblastoma

glioma

radiogenomics

radiomics

survival

Journal Article

0000-0002-6656-295X

10.1016/j.ccell.2018.06.006

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.

link

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

Cancer cell