Metb-04. Utility of Optical Genome Mapping in the Characterization of Paediatric Central Nervous System Tumours: Analysis of a Mono-Institutional Series of 26 Cases

BACKGROUND Optical Genome Mapping (OGM) is a recent platform which enables the detection of genome-wide balanced and unbalanced structural rearrangements (SR), providing a genome complexity overview. METHODS This study explores OGM implementation in the context of paediatric central nervous system (CNS) tumours by analyzing a series of 26 cases. RESULTS OGM equaled Chromosomal Microarray Analysis in detecting aneuploidies and copy number alterations (CNA), and, although less sensitive than RNAseq in identifying gene-fusions (15/19), enabled the definition of their causative mechanism. The assessment of SR and CNA allowed the distinction of different groups. Amount and distribution of SR identified 4 groups: HIGH_SR with >10 breakpoints (BP) distributed in ≥5 chromosomes (8 cases), SR_CHROMOTHRIPSIS with ≥10BP in <5 chromosomes with the most affected chromosome presenting with >10 BP (9 cases), and LOW_SR with <10BP (9 cases). CNA non-associated with chromothripsis (nCthCNA) stratified the series in NO_nCthCNA, LOW_nCthCNA, INT_nCthCNA, HIGH_nCthCNA group, where the alterations were absent (9 cases), <10 (9 cases), 10-49 (2 cases) and ≥50 (6 cases), respectively. nCthCNA directly correlated with the mean number of chromosomes harboring SR, i.e. 10.2 in HIGH_/INT_nCthCNA vs 2.5 in NO_/LOW_nCthCNA (p=0.001), and inversely with chromothripsis (9/18 in NO_/LOW_nCthCNA vs 0/8 in HIGH_/INT_nCthCNA, p=0.015). CONCLUSIONS High complexity groups associated with biological aggressiveness, with HIGH_nCthCNA including only high-grade tumours (p=0.004) and disease progression mostly occurring in HIGH_SR (6/7 cases vs 1/17, p<0.001) and HIGH_nCthCNA (4/5 vs 2/12 cases, p=0.013). Low-complexity groups were enriched of low/intermediate-grade tumours (13/15 in NO_/LOW_nCthCNA vs 5/11 in INT_/HIGH_nCthCNA, p=0.024). SR_CHROMOTHRIPSIS cases were all low/intermediate-grade fusion-driven tumours, did not harbour TP53 mutations or high-impact CNA (0/9 vs 7/17, p=0.030), and did not progress (0/9 vs 7/16, p=0.030). This study suggests a possible value of OGM assessment of genome complexity in prognostication of paediatric CNS tumours.