Frequency and Prognostic Impact of CDKN2A/B Alteration in Oligodendrogliomas: Systematic Review and Meta-analysis
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...
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The Japan Neurosurgical Society
2024-12-01
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| Series: | Neurologia Medico-Chirurgica |
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| Online Access: | https://www.jstage.jst.go.jp/article/nmc/64/12/64_2024-0105/_pdf/-char/en |
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| author | Satoshi NAKASU Shoichi DEGUCHI Yoko NAKASU |
| author_facet | Satoshi NAKASU Shoichi DEGUCHI Yoko NAKASU |
| author_sort | Satoshi NAKASU |
| collection | DOAJ |
| description | 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; I2 = 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. |
| format | Article |
| id | doaj-art-26d4075b86e44daaab3debfa96d0957f |
| institution | Kabale University |
| issn | 1349-8029 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | The Japan Neurosurgical Society |
| record_format | Article |
| series | Neurologia Medico-Chirurgica |
| spelling | doaj-art-26d4075b86e44daaab3debfa96d0957f2025-01-14T07:36:45ZengThe Japan Neurosurgical SocietyNeurologia Medico-Chirurgica1349-80292024-12-01641244245010.2176/jns-nmc.2024-01052024-0105Frequency and Prognostic Impact of CDKN2A/B Alteration in Oligodendrogliomas: Systematic Review and Meta-analysisSatoshi NAKASU0Shoichi DEGUCHI1Yoko NAKASU2Division of Neurosurgery, Omi Medical CenterDepartment of Neurosurgery, Nagoya University Graduate School of MedicineDepartment of Neurosurgery, Shiga University of Medical ScienceIsocitrate 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; I2 = 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.https://www.jstage.jst.go.jp/article/nmc/64/12/64_2024-0105/_pdf/-char/en1p/19q codeletioncdkn2a/bhomozygous deletionpromoter methylationoligodendroglioma |
| spellingShingle | Satoshi NAKASU Shoichi DEGUCHI Yoko NAKASU Frequency and Prognostic Impact of CDKN2A/B Alteration in Oligodendrogliomas: Systematic Review and Meta-analysis Neurologia Medico-Chirurgica 1p/19q codeletion cdkn2a/b homozygous deletion promoter methylation oligodendroglioma |
| title | Frequency and Prognostic Impact of CDKN2A/B Alteration in Oligodendrogliomas: Systematic Review and Meta-analysis |
| title_full | Frequency and Prognostic Impact of CDKN2A/B Alteration in Oligodendrogliomas: Systematic Review and Meta-analysis |
| title_fullStr | Frequency and Prognostic Impact of CDKN2A/B Alteration in Oligodendrogliomas: Systematic Review and Meta-analysis |
| title_full_unstemmed | Frequency and Prognostic Impact of CDKN2A/B Alteration in Oligodendrogliomas: Systematic Review and Meta-analysis |
| title_short | Frequency and Prognostic Impact of CDKN2A/B Alteration in Oligodendrogliomas: Systematic Review and Meta-analysis |
| title_sort | frequency and prognostic impact of cdkn2a b alteration in oligodendrogliomas systematic review and meta analysis |
| topic | 1p/19q codeletion cdkn2a/b homozygous deletion promoter methylation oligodendroglioma |
| url | https://www.jstage.jst.go.jp/article/nmc/64/12/64_2024-0105/_pdf/-char/en |
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