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

Purpose: To detect the epidermal growth factor receptor gene (EGFR) mutation profile and transcriptional variants in high-grade gliomas (HGGs), we sequenced EGFR and evaluated the EGFR splicing profile using a next-generation sequencing (NGS) oncopanel. Methods: We analyzed 124 HGGs—10 grade Ⅲ IDH-wildtype anaplastic astrocytomas (AAs) and 114 grade Ⅳ IDH-wildtype glioblastomas (GBMs). Results: The EGFR mutations were observed in 6.0% of grade Ⅳ GBMs and in 33% of grade Ⅲ AAs. Four cases harbored missense mutations in the EGFR kinase domain (L747A, S768I, V774M, and T790M). A total of 25% of the GBMs showed EGFR amplification. Moreover, 27% of the EGFR mutations occurred in the kinase domain. EGFRvⅢ positivity was detected in 8.0% of EGFR-amplified GBMs. We identified two other EGFR variants in GBM cases with deletions of exons 6–7 (Δe 6-7) (one case) and exons 2–14 (Δe 2-14) (two cases). Interestingly, in one case, the initial EGFRvIII mutation transformed into an EGFR Δe 2-14 mutation during recurrence. The frequency of EGFR alterations in our cohort was lower but the frequency of EGFR mutations in the kinase domain in our cohort was higher than that in The Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center cohorts. Conclusions: We suggested that the EGFR gene profiles of GBM differ among cohorts and identified rare EGFR variants with longitudinal and temporal transformations of EGFRvⅢ.