A case of glioblastoma harboring non-amplified epidermal growth factor receptor variant III: Critical molecular detection using RNA-based panel analysis

Amplification of the epidermal growth factor receptor gene ( EGFR ) and its variants are the most commonly detected pathogenic gene alterations in glioblastoma. Herein, we report a case of molecularly defined glioblastoma harboring an EGFR variant III ( EGFRvIII ) without EGFR amplification. The initial histological diagnosis was isocitrate dehydrogenase ( IDH )-wildtype low-grade glioma, due to an absence of anaplasia , necrosis, and microvascular proliferation, and a low Ki-67 labeling index. DNA-based next-generation sequencing (NGS) panel analysis revealed a TERTp promoter mutation but no EGFR mutation or amplification, supporting the diagnosis of "molecular glioblastoma." However, RNA-based NGS panel analysis revealed mRNA expression of EGFRvIII . Therefore, the final integrative diagnosis was glioblastoma with non-amplified EGFRvIII . Our report suggests that non-amplified EGFRvIII might be an early molecular event in glioblastoma tumorigenesis. In addition to the usual DNA-based analysis, RNA-based analysis is required to identify exon-skipping EGFR variants without EGFR amplification.