{"title":"利用纳米孔测序对IDH突变胶质瘤进行定性和分级","authors":"Thidathip Wongsurawat, Piroon Jenjaroenpun, Panatna Anekwiang, Tantip Arigul, Wichayapat Thongrattana, Azemat Jamshidi-Parsian, Gunnar Boysen, Prapat Suriyaphol, Bhoom Suktitipat, Prajak Srirabheebhat, Pornsuk Cheunsuchon, Jantima Tanboon, Intawat Nookaew, Sith Sathornsumetee","doi":"10.1111/bpa.13203","DOIUrl":null,"url":null,"abstract":"<p>The 2021 WHO Classification of Central Nervous System Tumors recommended evaluation of cyclin-dependent kinase inhibitor 2A/B (<i>CDKN2A/B</i>) deletion in addition to codeletion of 1p/19q to characterize <i>IDH-</i>mutant gliomas. Here, we demonstrated the use of a nanopore-based copy-number variation sequencing (nCNV-seq) approach to simultaneously identify deletions of <i>CDKN2A/B</i> and 1p/19q. The nCNV-seq approach was initially evaluated on three distinct glioma cell lines and then applied to 19 <i>IDH</i>-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 <i>CDKN2A/B</i> 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 (<i>r</i>) = 0.95, <i>P</i> < 2.2 × 10<sup>−16</sup> to <i>r</i> = 0.99, <i>P</i> < 2.2 × 10<sup>−16</sup>) and methylome profiling. Furthermore, nCNV-seq can differentiate between homozygous and hemizygous deletions of <i>CDKN2A/B</i>. Taken together, nCNV-seq holds promise as a new, alternative approach for a rapid and simultaneous detection of the molecular signatures of <i>IDH</i>-mutant gliomas without capital expenditure for a sequencer.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":null,"pages":null},"PeriodicalIF":5.8000,"publicationDate":"2023-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13203","citationCount":"1","resultStr":"{\"title\":\"Exploiting nanopore sequencing for characterization and grading of IDH-mutant gliomas\",\"authors\":\"Thidathip Wongsurawat, Piroon Jenjaroenpun, Panatna Anekwiang, Tantip Arigul, Wichayapat Thongrattana, Azemat Jamshidi-Parsian, Gunnar Boysen, Prapat Suriyaphol, Bhoom Suktitipat, Prajak Srirabheebhat, Pornsuk Cheunsuchon, Jantima Tanboon, Intawat Nookaew, Sith Sathornsumetee\",\"doi\":\"10.1111/bpa.13203\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The 2021 WHO Classification of Central Nervous System Tumors recommended evaluation of cyclin-dependent kinase inhibitor 2A/B (<i>CDKN2A/B</i>) deletion in addition to codeletion of 1p/19q to characterize <i>IDH-</i>mutant gliomas. Here, we demonstrated the use of a nanopore-based copy-number variation sequencing (nCNV-seq) approach to simultaneously identify deletions of <i>CDKN2A/B</i> and 1p/19q. The nCNV-seq approach was initially evaluated on three distinct glioma cell lines and then applied to 19 <i>IDH</i>-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 <i>CDKN2A/B</i> 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 (<i>r</i>) = 0.95, <i>P</i> < 2.2 × 10<sup>−16</sup> to <i>r</i> = 0.99, <i>P</i> < 2.2 × 10<sup>−16</sup>) and methylome profiling. Furthermore, nCNV-seq can differentiate between homozygous and hemizygous deletions of <i>CDKN2A/B</i>. Taken together, nCNV-seq holds promise as a new, alternative approach for a rapid and simultaneous detection of the molecular signatures of <i>IDH</i>-mutant gliomas without capital expenditure for a sequencer.</p>\",\"PeriodicalId\":9290,\"journal\":{\"name\":\"Brain Pathology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.8000,\"publicationDate\":\"2023-08-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13203\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/bpa.13203\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain Pathology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/bpa.13203","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 1
摘要
2021年《世界卫生组织中枢神经系统肿瘤分类》建议,除了评估1p/19q缺失代码外,还要评估细胞周期蛋白依赖性激酶抑制剂2A/B(CDKN2A/B)缺失,以确定IDH突变胶质瘤的特征。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)方法同时鉴定CDKN2A/B和1p/19q的缺失。nCNV-seq 方法首先在三种不同的胶质瘤细胞系上进行了评估,然后应用于来自患者的 19 个 IDH 突变胶质瘤(8 个星形细胞瘤和 11 个少突胶质瘤)。在所有少枝胶质瘤中都检测到了全臂 1p/19q 缺失,nCNV-seq、FISH、DNA 甲基化分析和全基因组测序结果高度一致。对于 CDKN2A/B 缺失,nCNV-seq 在星形细胞瘤和少突胶质瘤中都检测到了缺失,与全基因组测序(Pearson correlation (r) = 0.95, P < 2.2 × 10-16 to r = 0.99, P < 2.2 × 10-16)和甲基化组图谱得出的 CNV 图谱有很强的相关性。此外,nCNV-seq 还能区分 CDKN2A/B 的同卵缺失和半同卵缺失。综上所述,nCNV-seq有望成为一种新的替代方法,可在不花费测序仪费用的情况下快速、同步地检测IDH突变胶质瘤的分子特征。
Exploiting nanopore sequencing for characterization and grading of IDH-mutant gliomas
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 × 10−16 to r = 0.99, P < 2.2 × 10−16) 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.
期刊介绍:
Brain Pathology is the journal of choice for biomedical scientists investigating diseases of the nervous system. The official journal of the International Society of Neuropathology, Brain Pathology is a peer-reviewed quarterly publication that includes original research, review articles and symposia focuses on the pathogenesis of neurological disease.