Exploiting nanopore sequencing for characterization and grading of IDH‐mutant gliomas
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- Neurology (clinical)
- Pathology and Forensic Medicine
- General Neuroscience
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.