Glioma-specific Domain IV EGFR cysteine mutations promote ligand-induced covalent receptor dimerization and display enhanced sensitivity to dacomitinib in vivo
SA Greenall, JF Donoghue, NG Gottardo, TG Johns, TE Adams
ONCOGENE | NATURE PUBLISHING GROUP | Published : 2015
A feature of many gliomas is the amplification of the epidermal growth factor receptor (EGFR), resulting in its overexpression. Missense mutations or deletions within the extracellular domain are associated with this amplification and can lead to constitutive activation of the receptor, with the Domain I/II deletion, EGFRvIII, being the most common. These changes have also been associated with increased sensitivity to EGFR inhibition using small molecule inhibitors. We have expressed, in human glioma cells, EGFR containing four glioma-specific EGFR missense mutations within Domain IV (C620Y, C624F, C628Y and C636Y) to analyze their biological properties and sensitivity to EGFR inhibition. On..View full abstract
Awarded by NHMRC project
We would like to thank Professor Antony Burgess from the Walter and Eliza Hall Institute, Melbourne, Victoria for his critical review of the manuscript. SAG is supported by a CSIRO OCE Postdoctoral Fellowship. JFD is funded by a Cure Cancer Australia Foundation Postdoctoral Fellowship. TGJ was supported by NH&MRC project grants (1028552 and 1012020), the Victorian Government's Operational Infrastructure Support Program and Cure for Life Foundation.