Known disease-driving CNAs controlling multiple downstream hub genes could be identified, namely oncogenes and tumor suppressors with a known role in GBM, including EGFR, PDGFRA, CDKN2A, and CDKN2B, but also other interesting hub genes not previously associated with GBM, e.g., MTAP and SEC61G. The model also detected robust CNA–mRNA links between the hubs EGFR, PDGFRA, and CHIC2 and markers of early neural development, such as a GBM stem cell marker, CD133 (PROM1), and the transcription factors SOX10, SOX11, NR2E1 (TLX), and NKX2.2. Here, NKX2-2 is linked to glioblastoma.