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

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 EGFR v III . 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, EGFR v III displays low‐level constitutive signaling that is augmented by reduced internalization and downregulation. Aberrant EGFR v III signaling has been shown to be important in driving tumor progression and often correlates with poor prognosis. It is clear that EGFR v III is expressed in a considerable proportion of patients with glioblastoma multiforme ( GBM ). The presence of EGFR v III in other tumor types, however, remains controversial. In this review, we critically analyze the evidence for the expression of EGFR v III in a range of tumor types and discuss recent findings pertinent to its function and biology in GBM .