The epidermal growth factor receptor variant III (EGFRvIII): where wild things are altered

Hui K Gan, Anna Nada Cvrljevic, Terrance Grant Johns

Research output: Contribution to journalArticleResearchpeer-review

190 Citations (Scopus)


The epidermal growth factor receptor (EGFR) is overexpressed in a variety of human epithelial tumors, often as a consequence of gene amplification. Tumors with EGFR gene amplification frequently contain EGFR gene rearrangements, with the most common extracellular domain mutation being EGFRvIII. This mutation leads to a deletion of exons 2-7 of the EGFR gene and renders the mutant receptor incapable of binding any known ligand. Despite this, EGFRvIII displays low-level constitutive signaling that is augmented by reduced internalization and downregulation. Aberrant EGFRvIII signaling has been shown to be important in driving tumor progression and often correlates with poor prognosis. It is clear that EGFRvIII is expressed in a considerable proportion of patients with glioblastoma multiforme (GBM). The presence of EGFRvIII in other tumor types, however, remains controversial. In this review, we critically analyze the evidence for the expression of EGFRvIII in a range of tumor types and discuss recent findings pertinent to its function and biology in GBM.
Original languageEnglish
Pages (from-to)5350 - 5370
Number of pages21
JournalThe FEBS Journal
Issue number21
Publication statusPublished - 2013

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