EP12.10 HEMIZYGOUS DELETION OF CDKN2A/B IN IDH-MUTATED GLIOMA LEADS TO WORSE PROGNOSIS

Abstract BACKGROUND The negative prognostic impact of CDKN2A/B homozygous deletion in IDH-mutated glioma is well established. However, the prognostic significance of a hemizygous deletion remains debated. This study aims to evaluate overall survival (OS) and clinical characteristics of IDH-mutated gliomas with a hemizygous deletion of CKDN2A/B, compared to patients with retained status. MATERIAL AND METHODS This retrospective study defined the following inclusion criteria; (i) Operated at Sahlgrenska university hospital between 2007-2023 (ii) 18 years or older (iii) diagnosed with either an IDH-mutated astrocytoma or oligodendroglioma grade 2-3 according to the 2021 WHO classification system. CDKN2A/B status was determined through visual assessment of copy-number plots generated from DNA methylation data. The level of the CDKN2A/B locus was compared to baseline, whole chromosomal losses and extensive segmental losses to determine gene status. RESULTS A total of 198 patients were included; 97 astrocytomas and 101 oligodendrogliomas. A hemizygous deletion of CDKN2A/B was identified in 21 cases. These patients had a significantly shorter OS compared to those with retained CDKN2A/B (8 years vs. 14 years, p = 0.02). This difference was significant in astrocytomas (n = 12, 6 years vs. 11 years, p = 0.03) but not in oligodendrogliomas (n = 9, 10 years vs. not reached, p = 0.27). Tumors with a hemizygous CDKN2A/B deletion presented more frequently with headache and motor deficits. However, in a sensitivity analysis, the distribution of debut symptom was only significant in oligodendrogliomas. There were no other significant differences regarding tumor volume, surgical approach or oncological treatment. CONCLUSION A CDKN2A/B hemizygous deletion is associated with worse survival in IDH-mutated astrocytomas.