ETMR-03. Intra- and extra-cranial BCOR-ITD tumours are separate entities within the BCOR-rearranged family

BCOR-ITD tumours form an emerging family of aggressive entities with an internal tandem duplication (ITD) in the last exon of the BCOR gene. The family includes cerebral tumours, termed central nervous system BCOR-ITD (CNS BCOR-ITD), and sarcomatous types described in the kidney as clear cell sarcoma of the kidney (CCSK), in the endometrium as high-grade endometrial stromal sarcoma (HG-ESS), in bone, and in soft tissue as undifferentiated round cell sarcoma (URCS) or primitive myxoid mesenchymal tumour of infancy (PMMTI). Based on a series of 33 retrospective cases, including 10 CNS BCOR-ITD and 23 BCOR-ITD sarcomas, we interrogated the homogeneity of the entity regarding clinical, radiological and histopathological findings, and molecular signatures. Whole transcriptomic sequencing and DNA methylation profiling were used for unsupervised clustering. Histopathological review revealed marked differences between CNS BCOR-ITD and BCOR-ITD sarcomas. These two groups were consistently segregated by unsupervised clustering of expression (n=22) and DNA methylation (n=21) data. Proximity between the two groups may result from common somatic changes within key pathways directly related to the novel activity of the ITD itself. Conversely, comparison of gene signatures with single-cell RNAseq atlases suggests that the distinction between BCOR-ITD sarcomas and CNS BCOR-ITD may result from differences in cells of origin.