In GBM, EGFR mutations typically cluster in the extracellular domain and include in-frame deletions (such as the common “variant III” del 6-273) and missense mutations (A289V, A289D, T263P, G598V). However, the p.E709K mutation in the tyrosine kinase domain of EGFR has not been previously reported in GBM. In vitro functional characterization of mutations at E709 have been reported to be activivating mutations that are associated with sensitivity to EGFR inhibitors in vitro in some cell systems. The clinical significance of this mutation with regards to response to anti-EGFR therapy in GBM is unknown.
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