Use of Optical Genome Mapping to Detect Structural Variants in Neuroblastoma

Area of Science:

• Genomics
• Cancer Genetics
• Paediatric Oncology

Background:

• Neuroblastoma is a prevalent paediatric extracranial solid tumour, responsible for significant cancer mortality in children.
• Numerous genetic abnormalities are recognized as critical prognostic indicators in neuroblastoma.
• Optical genome mapping (OGM) is an emerging cytogenetic technology for structural variant detection, previously unevaluated in neuroblastoma.

Purpose of the Study:

• To apply OGM for identifying copy number and structural variants (SVs) in neuroblastoma.
• To detect SVs potentially missed by conventional cytogenetic techniques.

Main Methods:

• Analysis of five neuroblastoma cell lines and two neuroblastoma tumours using OGM on the Bionano Saphyr instrument.
• Comparison of OGM findings with established methods like G-band karyotyping, FISH, SNP array, and whole genome sequencing (WGS).

Main Results:

• OGM successfully identified copy number abnormalities previously detected by other methods, offering precise absolute copy number estimations for amplified genes.
• Novel SVs, including clinically relevant fusion genes in two cell lines, were discovered using OGM.

Conclusions:

• OGM demonstrates reliable detection of clinically significant structural and copy number variations in a single assay.
• OGM presents a potential advancement in time and cost-effectiveness compared to existing standard cytogenetic techniques for neuroblastoma analysis.