Division of Medical Bioinformatics, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Department of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Brain Pathol. 2024 Jan;34(1):e13203. doi: 10.1111/bpa.13203. Epub 2023 Aug 13.
The 2021 WHO Classification of Central Nervous System Tumors recommended evaluation of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion in addition to codeletion of 1p/19q to characterize IDH-mutant gliomas. Here, we demonstrated the use of a nanopore-based copy-number variation sequencing (nCNV-seq) approach to simultaneously identify deletions of CDKN2A/B and 1p/19q. The nCNV-seq approach was initially evaluated on three distinct glioma cell lines and then applied to 19 IDH-mutant gliomas (8 astrocytomas and 11 oligodendrogliomas) from patients. The whole-arm 1p/19q codeletion was detected in all oligodendrogliomas with high concordance among nCNV-seq, FISH, DNA methylation profiling, and whole-genome sequencing. For the CDKN2A/B deletion, nCNV-seq detected the loss in both astrocytoma and oligodendroglioma, with strong correlation with the CNV profiles derived from whole-genome sequencing (Pearson correlation (r) = 0.95, P < 2.2 × 10 to r = 0.99, P < 2.2 × 10 ) and methylome profiling. Furthermore, nCNV-seq can differentiate between homozygous and hemizygous deletions of CDKN2A/B. Taken together, nCNV-seq holds promise as a new, alternative approach for a rapid and simultaneous detection of the molecular signatures of IDH-mutant gliomas without capital expenditure for a sequencer.
2021 年世界卫生组织中枢神经系统肿瘤分类建议评估细胞周期蛋白依赖性激酶抑制剂 2A/B（CDKN2A/B）缺失，除了 1p/19q 缺失，以表征 IDH 突变型胶质瘤。在这里，我们展示了使用基于纳米孔的拷贝数变异测序（nCNV-seq）方法来同时识别 CDKN2A/B 和 1p/19q 的缺失。nCNV-seq 方法最初在三种不同的神经胶质瘤细胞系中进行了评估，然后应用于 19 例 IDH 突变型胶质瘤（8 例星形细胞瘤和 11 例少突胶质细胞瘤）患者。所有少突胶质细胞瘤均检测到全臂 1p/19q 缺失，nCNV-seq、FISH、DNA 甲基化分析和全基因组测序之间具有高度一致性。对于 CDKN2A/B 缺失，nCNV-seq 检测到星形细胞瘤和少突胶质细胞瘤均存在缺失，与全基因组测序（Pearson 相关系数（r）= 0.95，P < 2.2×10 至 r = 0.99，P < 2.2×10 ）和甲基组谱分析得出的 CNV 谱具有很强的相关性。此外，nCNV-seq 可以区分 CDKN2A/B 的纯合缺失和杂合缺失。总之，nCNV-seq 有望成为一种新的替代方法，用于快速且同时检测 IDH 突变型胶质瘤的分子特征，而无需为测序仪进行资本支出。
