Use of Optical Genome Mapping to Detect Structural Variants in Neuroblastoma

SIMPLE SUMMARY: Copy number abnormalities (CNAs) are frequent in neuroblastoma and used to determine treatments. Little is known about the role of structural variants (SVs) in disease progression. Optical genome mapping (OGM) uses label patterns to scan the genome which can be used to identify SVs in cancer. Currently, the detection of SVs still relies on standard cytogenetic techniques. We investigated the utility of OGM to detect SVs in neuroblastoma cell lines and tumours and compared it with standard cytogenetic techniques. OGM confirmed known CNAs and identified novel SVs of potential clinical significance. ABSTRACT: Background: Neuroblastoma is the most common extracranial solid tumour in children, accounting for 15% of paediatric cancer deaths. Multiple genetic abnormalities have been identified as prognostically significant in neuroblastoma patients. Optical genome mapping (OGM) is a novel cytogenetic technique used to detect structural variants, which has not previously been tested in neuroblastoma. We used OGM to identify copy number and structural variants (SVs) in neuroblastoma which may have been missed by standard cytogenetic techniques. Methods: Five neuroblastoma cell lines (SH-SY5Y, NBLW, GI-ME-N, NB1691 and SK-N-BE2(C)) and two neuroblastoma tumours were analysed using OGM with the Bionano Saphyr(®) instrument. The results were analysed using Bionano Access software and compared to previous genetic analyses including G-band karyotyping, FISH (fluorescent in situ hybridisation), single-nucleotide polymorphism (SNP) array and RNA fusion panels for cell lines, and SNP arrays and whole genome sequencing (WGS) for tumours. Results: OGM detected copy number abnormalities found using previous methods and provided estimates for absolute copy numbers of amplified genes. OGM identified novel SVs, including fusion genes in two cell lines of potential clinical significance. Conclusions: OGM can reliably detect clinically significant structural and copy number variations in a single test. OGM may prove to be more time- and cost-effective than current standard cytogenetic techniques for neuroblastoma.