Distribution and favorable prognostic implication of genomic EGFR alterations in IDH-wildtype glioblastoma

Nayuta Higa, Toshiaki Akahane, Taiji Hamada, Hajime Yonezawa, Hiroyuki Uchida, Ryutaro Makino, Shoji Watanabe, Tomoko Takajo, Seiya Yokoyama, Mari Kirishima, Kei Matsuo, Shingo Fujio, Ryosuke Hanaya, Akihide Tanimoto, Koji Yoshimoto

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


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.

Original languageEnglish
JournalCancer Medicine
Publication statusAccepted/In press - 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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