Translational significance of CDKN2A/B homozygous deletion in isocitrate dehydrogenase-mutant astrocytoma.

Abstract

Isocitrate dehydrogenase (IDH) 1 or 2 mutations confer a favorable prognosis compared to IDH-wildtype in astrocytoma, frequently denoting a lower grade malignancy. However, recent molecular profiling has identified specific aggressive tumor subgroups with clear clinical prognostic implications that are independent of histologic grading. The homozygous deletion of CDKN2A/B is the strongest implicated independent indicator of the poor prognosis within IDH-mutant astrocytoma, and the identification of this alteration in these lower histologic grade tumors transforms their biology toward an aggressive grade 4 phenotype clinically. CDKN2A/B homozygous deletion is now sufficient to define a grade 4 tumor in IDH-mutant astrocytomas regardless of histologic appearance, yet there are currently no effective molecularly informed targeted therapies for these tumors. The biological impact of CDKN2A/B homozygous deletion in IDH-mutant tumors and the optimal treatment strategy for this molecular subgroup remains insufficiently explored. Here we review the current understanding of the translational significance of homozygous deletion of CDKN2A/B gene expression in IDH-mutant astrocytoma and associated diagnostic and therapeutic implications.

• Authors: Shannon P Fortin Ensign, Robert B Jenkins, Caterina Giannini, Jann N Sarkaria, Evanthia Galanis, Sani H Kizilbash
• Journal: Neuro-oncology (Neuro Oncol) Vol. 25 Issue 1 Pg. 28-36 (01 05 2023) ISSN: 1523-5866 [Electronic] England
• PMID: 35973817 (Publication Type: Review, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• CDKN2A protein, human
• Cyclin-Dependent Kinase Inhibitor p16
• Isocitrate Dehydrogenase
• CDKN2B protein, human

Topics

• Humans
• Astrocytoma (pathology)
• Brain Neoplasms (pathology)
• Cyclin-Dependent Kinase Inhibitor p16 (genetics, metabolism)
• Homozygote
• Isocitrate Dehydrogenase (genetics)
• Mutation
• Sequence Deletion