<i>CDKN2A</i> Homozygous Deletion Is a Stronger Predictor of Outcome than <i>IDH1/2</i>-Mutation in CNS WHO Grade 4 Gliomas
<b>Background</b>: We primarily investigated the prognostic role of <i>CDKN2A</i> homozygous deletion in CNS WHO grade 4 gliomas. Additionally, we plan to examine traditional prognostic factors for grade 4 gliomas and validate the findings. <b>Materials</b>: We co...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-10-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/12/10/2256 |
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| Summary: | <b>Background</b>: We primarily investigated the prognostic role of <i>CDKN2A</i> homozygous deletion in CNS WHO grade 4 gliomas. Additionally, we plan to examine traditional prognostic factors for grade 4 gliomas and validate the findings. <b>Materials</b>: 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 <i>IDH1/2</i> mutation and <i>CDKN2A</i> deletion using NGS analysis with ONCOaccuPanel<sup>®</sup>. Further, we examined traditional prognostic factors, including age, WHO performance status, extent of resection, and <i>MGMT</i> promoter methylation status. <b>Results</b>: 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, <i>IDH</i>-mutant, and CNS WHO grade 4 cases, and 107 (78.7%) glioblastoma, <i>IDH</i>-wildtype, and CNS WHO grade 4 cases. Among them, 61 (56.0%) had <i>CDKN2A</i> deletions. The high-risk group with <i>CDKN2A</i> deletion regardless of <i>IDH1/2</i> mutation had a mean OS of 16.65 months (SD, ±1.554), the intermediate-risk group without <i>CDKN2A</i> deletion and with <i>IDH1/2</i> mutation had a mean OS of 21.85 months (SD, ±2.082), and the low-risk group without CDKN2A deletion and with <i>IDH1/2</i> 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), <i>MGMT</i> promoter methylation, (methylated vs. unmethylated; HR 5.078), <i>IDH1/2</i> mutation (mutant vs. wildtype; HR 6.352), and <i>CDKN2A</i> deletion (absence vs. presence; HR 13.454) were associated with OS independently. <b>Conclusions</b>: The present study suggests that <i>CDKN2A</i> deletion plays a powerful prognostic role in CNS WHO grade 4 gliomas. Even if CNS WHO grade 4 gliomas have mutant <i>IDH1/2</i>, they may have poor clinical outcomes because of <i>CDKN2A</i> deletion. |
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| ISSN: | 2227-9059 |