Distribution and favorable prognostic implication of genomic <scp><i>EGFR</i></scp> alterations in <scp><i>IDH</i></scp>‐wildtype glioblastoma

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>We aimed to evaluate the mutation profile, transcriptional variants, and prognostic impact of the epidermal growth factor receptor (<jats:italic>EGFR</jats:italic>) gene in isocitrate dehydrogenase (<jats:italic>IDH</jats:italic>)‐wildtype glioblastomas (GBMs).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We sequenced <jats:italic>EGFR</jats:italic>, evaluated the <jats:italic>EGFR</jats:italic> splicing profile using a next‐generation sequencing oncopanel, and analyzed the outcomes in 138 grade IV <jats:italic>IDH</jats:italic>‐wildtype GBM cases.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:italic>EGFR</jats:italic> mutations were observed in 10% of GBMs. A total of 23.9% of the GBMs showed <jats:italic>EGFR</jats:italic> amplification. Moreover, 25% of the <jats:italic>EGFR</jats:italic> mutations occurred in the kinase domain. Notably, <jats:italic>EGFR</jats:italic> alterations were a predictor of good prognosis (<jats:italic>p</jats:italic> = 0.035). GBM with <jats:italic>EGFR</jats:italic> alterations was associated with higher Karnofsky Performance Scale scores (<jats:italic>p</jats:italic> = 0.014) and lower Ki‐67 scores (<jats:italic>p</jats:italic> = 0.005) than GBM without <jats:italic>EGFR</jats:italic> alterations. <jats:italic>EGFRvIII</jats:italic> positivity was detected in 21% of <jats:italic>EGFR</jats:italic>‐amplified GBMs. We identified two other <jats:italic>EGFR</jats:italic> variants in GBM cases with deletions of exons 6–7 (Δe 6–7) and exons 2–14 (Δe 2–14). In one case, the initial <jats:italic>EGFRvIII</jats:italic> mutation transformed into an <jats:italic>EGFR</jats:italic> Δe 2–14 mutation during recurrence.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>We found that the <jats:italic>EGFR</jats:italic> gene profiles of GBM differ among cohorts and that <jats:italic>EGFR</jats:italic> alterations are good prognostic markers of overall survival in patients with <jats:italic>IDH</jats:italic>‐wildtype GBM. Additionally, we identified rare <jats:italic>EGFR</jats:italic> variants with longitudinal and temporal transformations of <jats:italic>EGFRvIII</jats:italic>.</jats:p></jats:sec>