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

Zev A. Binder; Amy Haseley Thorne; Spyridon Bakas; E. Paul Wileyto; Michel Bilello; Hamed Akbari; Saima Rathore; Sung Min Ha; Logan Zhang; Cole J. Ferguson; Sonika Dahiya; Wenya Linda Bi; David A. Reardon; Ahmed Idbaih; Joerg Felsberg; Bettina Hentschel; Michael Weller; Stephen J. Bagley; Jennifer J.D. Morrissette; MacLean P. Nasrallah; Jianhui Ma; Ciro Zanca; Andrew M. Scott; Laura Orellana; Christos Davatzikos; Frank B. Furnari; Donald M. O'Rourke

doi:10.1016/j.ccell.2018.06.006

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

Zev A. Binder, Amy Haseley Thorne, Spyridon Bakas, E. Paul Wileyto, Michel Bilello, Hamed Akbari, Saima Rathore, Sung Min Ha, Logan Zhang, Cole J. Ferguson, Sonika Dahiya, Wenya Linda Bi, David A. Reardon, Ahmed Idbaih, Joerg Felsberg, Bettina Hentschel, Michael Weller, Stephen J. Bagley, Jennifer J.D. Morrissette, MacLean P. NasrallahJianhui Ma, Ciro Zanca, Andrew M. Scott, Laura Orellana, Christos Davatzikos, Frank B. Furnari, Donald M. O'Rourke

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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 (EGFR^A289D/T/V). Quantitative multi-parametric magnetic resonance imaging analyses indicated increased tumor invasion for EGFR^A289D/T/V mutants, corroborated in mice bearing intracranial tumors expressing EGFR^A289V and dependent on ERK-mediated expression of matrix metalloproteinase-1. EGFR^A289V 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^A289V mutation in glioblastoma, postulating EGFR^A289V as a molecular marker for responsiveness to therapy with EGFR-targeting antibodies.

Original language	English
Pages (from-to)	163-177.e7
Journal	Cancer Cell
Volume	34
Issue number	1
DOIs	https://doi.org/10.1016/j.ccell.2018.06.006
State	Published - Jul 9 2018

Keywords

A289D/T/V
EGFR
EGFR oncogenes
EGFR targeted therapy
GBM
glioblastoma
glioma
radiogenomics
radiomics
survival

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10.1016/j.ccell.2018.06.006

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Binder, Z. A., Thorne, A. H., Bakas, S., Wileyto, E. P., Bilello, M., Akbari, H., Rathore, S., Ha, S. M., Zhang, L., Ferguson, C. J., Dahiya, S., Bi, W. L., Reardon, D. A., Idbaih, A., Felsberg, J., Hentschel, B., Weller, M., Bagley, S. J., Morrissette, J. J. D., ... O'Rourke, D. M. (2018). Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development. Cancer Cell, 34(1), 163-177.e7. https://doi.org/10.1016/j.ccell.2018.06.006

@article{5e22b7619166477d99e4736a2f78afc2,

title = "Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development",

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.",

keywords = "A289D/T/V, EGFR, EGFR oncogenes, EGFR targeted therapy, GBM, glioblastoma, glioma, radiogenomics, radiomics, survival",

author = "Binder, {Zev A.} and Thorne, {Amy Haseley} and Spyridon Bakas and Wileyto, {E. Paul} and Michel Bilello and Hamed Akbari and Saima Rathore and Ha, {Sung Min} and Logan Zhang and Ferguson, {Cole J.} and Sonika Dahiya and Bi, {Wenya Linda} and Reardon, {David A.} and Ahmed Idbaih and Joerg Felsberg and Bettina Hentschel and Michael Weller and Bagley, {Stephen J.} and Morrissette, {Jennifer J.D.} and Nasrallah, {MacLean P.} and Jianhui Ma and Ciro Zanca and Scott, {Andrew M.} and Laura Orellana and Christos Davatzikos and Furnari, {Frank B.} and O'Rourke, {Donald M.}",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2018",

month = jul,

day = "9",

doi = "10.1016/j.ccell.2018.06.006",

language = "English",

volume = "34",

pages = "163--177.e7",

journal = "Cancer Cell",

issn = "1535-6108",

number = "1",

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Binder, ZA, Thorne, AH, Bakas, S, Wileyto, EP, Bilello, M, Akbari, H, Rathore, S, Ha, SM, Zhang, L, Ferguson, CJ, Dahiya, S, Bi, WL, Reardon, DA, Idbaih, A, Felsberg, J, Hentschel, B, Weller, M, Bagley, SJ, Morrissette, JJD, Nasrallah, MP, Ma, J, Zanca, C, Scott, AM, Orellana, L, Davatzikos, C, Furnari, FB & O'Rourke, DM 2018, 'Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development', Cancer Cell, vol. 34, no. 1, pp. 163-177.e7. https://doi.org/10.1016/j.ccell.2018.06.006

TY - JOUR

T1 - Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development

AU - Binder, Zev A.

AU - Thorne, Amy Haseley

AU - Bakas, Spyridon

AU - Wileyto, E. Paul

AU - Bilello, Michel

AU - Akbari, Hamed

AU - Rathore, Saima

AU - Ha, Sung Min

AU - Zhang, Logan

AU - Ferguson, Cole J.

AU - Dahiya, Sonika

AU - Bi, Wenya Linda

AU - Reardon, David A.

AU - Idbaih, Ahmed

AU - Felsberg, Joerg

AU - Hentschel, Bettina

AU - Weller, Michael

AU - Bagley, Stephen J.

AU - Morrissette, Jennifer J.D.

AU - Nasrallah, MacLean P.

AU - Ma, Jianhui

AU - Zanca, Ciro

AU - Scott, Andrew M.

AU - Orellana, Laura

AU - Davatzikos, Christos

AU - Furnari, Frank B.

AU - O'Rourke, Donald M.

PY - 2018/7/9

Y1 - 2018/7/9

N2 - 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.

AB - 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.

KW - A289D/T/V

KW - EGFR

KW - EGFR oncogenes

KW - EGFR targeted therapy

KW - GBM

KW - glioblastoma

KW - glioma

KW - radiogenomics

KW - radiomics

KW - survival

UR - http://www.scopus.com/inward/record.url?scp=85049011855&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2018.06.006

DO - 10.1016/j.ccell.2018.06.006

M3 - Article

C2 - 29990498

AN - SCOPUS:85049011855

SN - 1535-6108

VL - 34

SP - 163-177.e7

JO - Cancer Cell

JF - Cancer Cell

IS - 1

ER -

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

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Keywords

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