BCOR Mutations Identify a Clinically Aggressive Subset of Pediatric Rhabdomyosarcoma

Background:BCOR mutations occur in about 5% in pediatric rhabdomyosarcoma (RMS), their clinical significance and mechanistic roles remain undefined. This study characterizes BCOR-mutant RMS as a molecularly distinct, high-risk subgroup. Methods: Multimodal analysis of four pediatric embryonal RMS cases with BCOR mutations, integrating histopathology, immunohistochemistry, genomic profiling, and clinical outcomes. Results: All patients (ages 1.9-11 years) presented with stage IV fusion-negative ERMS. Histology ranged from conventional (Cases 1,2,4) to undifferentiated (Case 3). IHC revealed: Universal MyoD1 nuclear positivity (70-95%), variable myogenin (5-50%). BCOR protein status potentially related to mutation VAF (15.1-96.16%): aberrant cytoplasmic staining with loss of nuclear expression in frameshift mutants (Case 3) vs. partial retention or completely loss in missense mutants (Cases 1,2,4). Molecular profiling identified recurrent co-alterations (TP53, MDM2/MYC). Despite multimodal therapy, all patients progressed (median EFS 16.5 months), with poorest outcomes in older children (Cases 1,3,4). Conclusions: BCOR mutations may define an aggressive RMS subtype in pediatric group.