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.

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