Spatial genomic heterogeneity in IDH-wildtype glioblastoma uncovered by multiregional analysis

A 58-year-old male presented with symptoms of apathy, inability to work.MRI revealed a contrast-enhancing lesion of the left frontal lobe.En bloc resection of the tumor was performed, including adjacent normal-appearing tissue.Molecular pathological diagnosis confirmed glioblastoma, IDH-wildtype.Following a detailed pathological review, three anatomically distinct regions were selected for genomic analysis based on histopathological differences as determined by board-certified pathologists (Figure 1):1. Peritumoral area, where no apparent tumor cells were observed histologically 2. Region with mild cytological atypia, corresponding to a WHO Grade 2 lesion 3. Region with marked cytological atypia, consistent with a WHO Grade 4 lesion Targeted next-generation sequencing was performed using the Rapid-Neo cancer gene panel (Sysmex Corporation, Kobe, Japan), which covers over 160 cancer-related genes associated with actionable targets.The genomic alterations identified in each region were as follows (Table 1): Region (peritumoral area): Actionable alterations: EGFR mutation and amplification Variants of Unknown Significance (VUS): MDM4 amplification Region (Grade 2-equivalent lesion)