Whole-genome insights: nanopore sequencing in neuropathology

Biography

Dr Skarphedinn Halldorsson is a senior researcher in the Vilhelm Magnus Laboratory, Department of Neurosurgery, Oslo University Hospital, Norway. His research interests focus on improving molecular diagnostics and treatment options for CNS cancer patients.

Abstract

Recent medical advances have significantly deepened our molecular understanding of cancers. However, cancer classification is increasingly complex, often requiring extensive molecular profiling for accurate diagnosis and identifying treatable targets. In neuropathology, comprehensive analyses, including point mutations, structural variants, chromosomal aberrations, and epigenetic profiling are common. Current methods rely on multiple platforms, which are costly, time-consuming, and may delay diagnosis and treatment. To address these challenges, we performed nanopore whole-genome sequencing (nWGS) on 78 brain tumor biopsies using PromethION Flow Cells. This approach identified all diagnostically and therapeutically relevant alterations, including methylation-based classification, gross chromosomal aberrations, gene amplifications and deletions, gene fusions, and single nucleotide variants (SNVs). The results were compared to the standard of care (SoC) at Oslo University Hospital, which involves various methods such as Sanger sequencing, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, next-generation sequencing panels, pyrosequencing, and EPIC beadchip methylation profiling. nWGS identified diagnostically relevant alterations in 75 of 78 samples (96.1%). Two cases were reclassified based on nWGS findings according to the current central nervous system (CNS) World Health Organization classification. The fastest turnaround from DNA extraction to a full genomic report was 4.5 days. nWGS offers a complete and efficient solution for detecting diagnostically and therapeutically relevant alterations. It also enables retrospective reclassification without additional testing, potentially replacing current genomic methods in molecular neuropathology with superior completeness, cost-effectiveness, and speed.