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Abstract
Introduction. Sarcomas with BCOR genetic alteration represent a relatively recently characterized group of tumors defined by aberrations in the BCOR gene that drive its oncogenic activation. These sarcomas exhibit diverse clinical behavior distinct from Ewing sarcoma (ES), despite sharing certain morphological similarities with ES. While morphological diagnosis proves accurate in the overwhelming majority of cases, confirmation often requires employment of diverse molecular diagnostic methods to detect direct or surrogate diagnostic markers.
Material and Methods. The study cohort comprised 23 patients with molecularly confirmed sarcomas with BCOR genetic alteration, diagnosed using RT-PCR, RNA sequencing, or Nanostring digital RNA barcoding. Clinical data for all patients were analyzed, and overall survival (OS) and event-free survival (EFS) rates were stratified by treatment protocol and assessed with the Kaplan-Meier method.
Results. Among 23 patients, sarcoma with BCOR genetic alteration was the initial morphological diagnosis in 22 cases (96%), while one patient (4%) was diagnosed with undifferentiated small round cell sarcoma (USRCS). Morphological diagnosis was molecularly confirmed in 17/23 cases via RT-PCR. In two cases with borderline RNA quality, confirmation was achieved using Nanostring digital RNA barcoding. The remaining four cases were validated through high-throughput sequencing, revealing rarer aberrations: BCOR ITD (ex15), BCOR::MAML3 (ex15::ex2) and YWHAE::NUTM2B (ex5::ex2). Median age at diagnosis was 10.5 years (range: 0.25–16.4). Localized disease was diagnosed in 17 patients (74%), and distant metastases were found in 6 patients (26%). Treatment protocols used were Euro-Ewing 2008/2012 regimens: 13 patients (57%), and CWS-2009 protocol: 10 patients (43%). Recurrence occurred in 8 patients (35%; 6 local, 2 systemic). 3-year OS was 96.0 ± 0.04% and 3-year EFS was 66.8 ± 0.12%.
Conclusion. Patients with the most frequent BCOR::CCNB3 rearrangement exhibit an indolent disease course, predilection for axial skeletal bones, and male predominance. Comparative analysis revealed no statistically significant difference in EFS between patients treated with Ewing-oriented protocols vs. those receiving soft tissue sarcoma treatment protocols.
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