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

CONTEXT.—: 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.

OBJECTIVE.—: To compare the pediatric BCL6 corepressor (BCOR) and capicua transcriptional repressor (CIC) sarcomas clinically while assessing the utility of advanced diagnostic algorithms.

DESIGN.—: 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.

RESULTS.—: 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%.

CONCLUSIONS.—: 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.