Pediatric Sarcomas With BCOR and CIC Aberrations: Advanced Diagnosis and Treatment Outcomes.

Abstract

Undifferentiated round cell sarcomas (URCSs) are tumors of bone and soft tissue that are heterogeneous in terms of driver events and diverse in their clinical course. To compare the pediatric BCL6 corepressor (BCOR) and capicua transcriptional repressor (CIC) sarcomas clinically while assessing the utility of advanced diagnostic algorithms. Forty-two histologically diagnosed undifferentiated round cell sarcomas were molecularly characterized using polymerase chain reaction assay, RNA sequencing, and/or NanoString digital bar code technology. The diagnosis of BCOR sarcoma was confirmed in 23 cases, including 17 cases of BCOR::cyclin B3 (CCNB3), 2 cases of BCOR internal tandem duplication, and single cases of BCOR::mastermind like transcriptional coactivator 3 (MAML3) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (YWHAE)::NUT family member 2B (NUTM2B); in 2 cases, the verification was based on gene expression profiles. The primary lesion was localized intraosseously (15 cases; 65%) or originated from soft tissues (8 cases; 35%). Three-year overall survival was 96.0% ± 0.04%. The diagnosis of CIC sarcoma was confirmed in 14 cases, including 5 cases of CIC::double homeobox 4 (DUX4), 4 cases of CIC exon 21 fused to an intergenic region, 2 cases of CIC::double homeobox 4 like 9 (pseudogene) (DUX4L9) and 1 case of CIC::NUTM2B; in 2 cases, verification was based on gene expression profiles. The primary lesion was localized in soft tissues (12 cases; 86%) or intraosseously (2 cases; 14%). Three-year overall survival was 34.4% ± 16.0%. Despite the relatively favorable outcomes in BCOR sarcomas, the relapse rate is considerable, whereas pediatric patients with CIC sarcoma typically develop metastatic disease and have poor outcomes. The data provide a prospective foundation for genetically based therapeutic strategies and risk stratification.