Hemizygous deletion of CDKN2A/B in IDH -mutated glioma: Prognostic impact when adjusting for clinical factors

Abstract Background There is inconsistent evidence if hemizygous CDKN2A/B deletion affects survival in IDH-mutated glioma, and clinical characteristics are rarely accounted for. This study aims to investigate overall survival and clinical characteristics of IDH-mutated glioma with a hemizygous deletion of CDKN2A/B. Method A total of 215 consecutive patients with IDH-mutated glioma, WHO grade 2 and 3, who underwent primary surgery between 2007 and 2023 in a defined catchment area were included. CDKN2A/B status was determined through visual assessment of DNA methylation array-derived copy-number plots. Multivariable analyses and propensity score matching were performed to consider other clinical factors. Results A CDKN2A/B hemizygous deletion was identified in 24/215 patients, including 22/116 with astrocytoma and 2/99 with oligodendroglioma. Due to this imbalance across subtypes, we primarily focused on astrocytomas. Hemizygous deletion was present in 9/65 patients with WHO grade 2 and 13/51 with WHO grade 3 astrocytomas. Patients with astrocytoma and hemizygous CDKN2A/B deletion had shorter overall survival compared to patients with intact CDKN2A/B status (5.8 years vs 11.4 years, P = .04). CDKN2A/B was a survival predictor in WHO grade 2 astrocytoma but not in WHO grade 3. However, these effects disappeared both in the multivariable analysis and in the propensity-matched cohort. Conclusion The presence of a hemizygous CDKN2A/B deletion occurs more frequently in astrocytomas compared to oligodendrogliomas at the time of primary diagnosis. Worse survival in patients with astrocytoma and CDKN2A/B hemizygous loss was observed, specifically in WHO grade 2, but this prognostic effect disappeared when adjusting for clinical factors.