Exploiting nanopore sequencing for characterization and grading of IDH-mutant gliomas
Issued Date
2023-01-01
Resource Type
ISSN
10156305
eISSN
17503639
Scopus ID
2-s2.0-85167676165
Journal Title
Brain Pathology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Brain Pathology (2023)
Suggested Citation
Wongsurawat T. Exploiting nanopore sequencing for characterization and grading of IDH-mutant gliomas. Brain Pathology (2023). doi:10.1111/bpa.13203 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/88377
Title
Exploiting nanopore sequencing for characterization and grading of IDH-mutant gliomas
Author(s)
Author's Affiliation
Other Contributor(s)
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.