Homozygous Deletion Is a Stronger Predictor of Outcome than -Mutation in CNS WHO Grade 4 Gliomas.

: We primarily investigated the prognostic role of homozygous deletion in CNS WHO grade 4 gliomas. Additionally, we plan to examine traditional prognostic factors for grade 4 gliomas and validate the findings. : We conducted a retrospective analysis of the glioma cohorts at our institute. We reviewed medical records spanning a 15-year period and examined pathological slides for an updated diagnosis according to the 2021 WHO classification of CNS tumors. We examined the mutation and deletion using NGS analysis with ONCOaccuPanel. Further, we examined traditional prognostic factors, including age, WHO performance status, extent of resection, and promoter methylation status. : The mean follow-up duration was 27.5 months (range: 4.1-43.5 months) and mean overall survival (OS) was 20.7 months (SD, ±1.759). After the exclusion of six patients with a poor status of pathologic samples, a total of 136 glioblastoma cases diagnosed by previous WHO classification criteria were newly classified into 29 (21.3%) astrocytoma, -mutant, and CNS WHO grade 4 cases, and 107 (78.7%) glioblastoma, -wildtype, and CNS WHO grade 4 cases. Among them, 61 (56.0%) had deletions. The high-risk group with deletion regardless of mutation had a mean OS of 16.65 months (SD, ±1.554), the intermediate-risk group without deletion and with mutation had a mean OS of 21.85 months (SD, ±2.082), and the low-risk group without CDKN2A deletion and with mutation had a mean OS of 33.38 months (SD, ±2.946). Multifactor analysis showed that age (≥50 years vs. <50 years; HR 4.645), WHO performance (0, 1 vs. 2; HR 5.002), extent of resection (gross total resection vs. others; HR 5.528), promoter methylation, (methylated vs. unmethylated; HR 5.078), mutation (mutant vs. wildtype; HR 6.352), and deletion (absence vs. presence; HR 13.454) were associated with OS independently. : The present study suggests that deletion plays a powerful prognostic role in CNS WHO grade 4 gliomas. Even if CNS WHO grade 4 gliomas have mutant , they may have poor clinical outcomes because of deletion.