10190-MPC-14 ANALYSIS OF GENETIC ABNORMALITIES IN TERTP-WILDTYPE MOLECULAR GBM

Abstract

Abstract Glioblastoma (GBM) is frequently linked to TERTp mutations. However, even in cases without these mutations, genetic alterations such as EGFR amplification or chromosome7 amplification/ chromosome10 deletion can lead to GBM diagnosis. In this study, we compared genetic differences between these molecularly characterized GBM (molGBM) cases and GBM cases without these features, focusing on 26 GBM cases lacking IDH and TERTp mutations from January 2016 to February 2022. Using Multiplex Ligation-dependent Probe Amplification (MLPA), we examined copy number changes in key genes (PDGFRA, EGFR, CDKN2A, PTEN, TP53, CDK4, MIR26A2, MDM2, NFKBIA). The thresholds for copy number changes were homozygous deletion (x≤0.4), loss of heterozygosity (LOH) (0.4<x≤0.7), gain (1.3≤x<2.0), amplification (x≥2.0). If PTEN LOH was present, it was considered chromosome10 deletion. Among the 26 cases, three were diagnosed as molGBM: two with EGFR amplification and one with chromosome7 amplification/ chromosome10 deletion. The remaining 23 had pathological GBM diagnoses. Notably, some cases showed amplifications in PDGFRA, CDK4, and MIR26A2, as well as LOH in TP53. In the control group, amplifications in PDGFRA, CDK4, MIR26A2, and LOH in TP53, CDKN2A, and MIR26A2 were observed. The genetic abnormalities observed in the molGBM group were similar to those in the control group. Further studies should clarify the correlation between these genetic abnormalities and the molecular GBM signature and their clinical significance.