{"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}
引用次数: 1
Abstract
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.