The prognostic impact of CDKN2A/B hemizygous deletions in IDH-mutant glioma.

Autor:	Ippen FM; University Hospital Heidelberg, Dept. of Neurology, Heidelberg, Germany.; German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany.; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and University Hospital Heidelberg, Germany., Hielscher T; Department of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany., Friedel D; German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany.; University Hospital Heidelberg, Dept. of Neuropathology, Heidelberg, Germany.; Faculty of Bioscience, Heidelberg University, 69120 Heidelberg, Germany., Göbel K; German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany.; University Hospital Heidelberg, Dept. of Neuropathology, Heidelberg, Germany., Reuss D; German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany.; University Hospital Heidelberg, Dept. of Neuropathology, Heidelberg, Germany., Herold-Mende C; University Hospital Heidelberg, Dept. of Neurosurgery, Division of Experimental Neurosurgery, Heidelberg, Germany.; University Hospital Heidelberg, Dept. of Neurosurgery, Heidelberg, Germany., Krieg S; University Hospital Heidelberg, Dept. of Neurosurgery, Heidelberg, Germany., Deimling AV; German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany.; University Hospital Heidelberg, Dept. of Neuropathology, Heidelberg, Germany., Wick W; University Hospital Heidelberg, Dept. of Neurology, Heidelberg, Germany.; German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neurooncology, Heidelberg, Germany., Sahm F; German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany.; University Hospital Heidelberg, Dept. of Neuropathology, Heidelberg, Germany., Suwala AK; German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany.; University Hospital Heidelberg, Dept. of Neuropathology, Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	Neuro-oncology [Neuro Oncol] 2024 Nov 12. Date of Electronic Publication: 2024 Nov 12.
DOI:	10.1093/neuonc/noae238
Abstrakt:	Background: Homozygous deletions of CDKN2A/B are known to predict poor prognosis in gliomas, but the impact of hemizygous deletions is less clear. This study aimed to evaluate the prognostic significance of hemizygous CDKN2A/B deletions in IDH-mutant low-grade astrocytomas and oligodendrogliomas. Methods: Tissue samples diagnosed as astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant, 1p/19q co-deleted CNS WHO grade 2 and 3 were collected from the archives of the Institute of Neuropathology in Heidelberg. DNA methylation analysis was performed on formalin-fixed paraffin-embedded (FFPE) samples. Evaluation of the CDKN2A/B locus was performed by visual inspection of copy-number plots derived from methylation-array data for each case. Hemizygous and homozygous losses were assessed in relation to whole chromosomal or larger segmental losses and gains in the chromosomal profile. Survival probabilities were assessed using the Kaplan-Meier method. Results: A total of 334 low-grade glioma cases were identified, including 173 astrocytomas and 161 oligodendrogliomas. Hemizygous deletions in CDKN2A/B (37/173 in astrocytomas, 15/161 in oligodendrogliomas) did not confer significantly worse survival outcomes compared to CDKN2A/B wildtype cases in neither low grade astrocytoma (log-rank p= 0.2556; HR 2.29, 95% CI [0.76; 6.40], p= 0.135) nor oligodendroglioma (log-rank p= 0.2760; HR 0.17; 95% CI [0.01; 5.05]; p= 0.305), regardless of CNS WHO grade, which was further demonstrated on a subgroup of astrocytoma, IDH mutant CNS WHO 4 cases (log-rank p= 0.1680; HR 4.55, 95% CI [0.88; 24.51], p= 0.0689). Conclusions: Hemizygous CDKN2A/B deletions do not significantly worsen OS or PFS in IDH-mutant astrocytomas and oligodendrogliomas, CNS WHO grade 2 and 3. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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