Frequency and Prognostic Impact of CDKN2A/B Alteration in Oligodendrogliomas: Systematic Review and Meta-analysis

Overview

Journal Neurol Med Chir (Tokyo)

Specialties Neurology
Neurosurgery

Date 2024 Oct 23

PMID 39443123

Authors

Satoshi Nakasu

Shoichi Deguchi

Yoko Nakasu

Affiliations

Soon will be listed here.

Abstract

Isocitrate dehydrogenase (IDH) -mutant astrocytomas with homozygous deletion of cyclin-dependent kinase 2A/B (CDKN2A/B-HomoD) are categorized to grade 4 in the new World Health Organization (WHO) classification. However, the clinical implications of CDKN2A/B-HomoD in oligodendrogliomas remain unclear. This study systematically reviewed and meta-analyzed the literature on molecularly defined oligodendrogliomas (mOlig) to find the frequency and prognostic significance of CDKN2A/B gene alterations. Overall survival was worse in patients with CDKN2A/B-HomoD [pooled hazard ratio (pHR) 2.44; 95% confidential interval (CI), 1.59-3.76; P < 0.0001; 7 studies, 1,012 patients] than in those without CDKN2A/B-HomoD. Although the frequency (95% CI) was very low in grade 2 tumors (0.31%; 0.02-0.4) than in grade 3 tumors (9.4%; 6.2-14.0; I = 52.0%), pHR of multivariate analyses with covariates of WHO grade and age was still significant (P = 0.017). In contrast, the method in CDKN2A/B evaluation was a significant factor for the heterogeneity in frequency. The pooled frequency of CDKN2A/B-HomoD in grade 3 mOlig by fluorescence in situ hybridization (FISH) (20.3%) was higher than that by other methods (7.3%; P < 0.0006), probably due to the lower threshold for CDKN2A/B-HomoD in FISH studies that was used in this analysis. The frequency (95% CI) of other alterations of the CDKN2A/B gene, i.e., mutation, hemizygous deletion, and promoter methylation, was estimated as 1.48% (0.6-3.5), 15.9% (9.8-24.7), and 20.6% (13.7-29.8), respectively. The clinical significance of these alterations remains unclear due to the immaturity of the investigations.

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