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Chromatin Remodeling and Cancer · Journal article
International Journal of Molecular Sciences · August 12, 2026
Early or partial results. Treat as a signal, not a conclusion.
This retrospective biobank study reports that NGS molecular profiling identified clinically relevant alterations in 70% of 55 pediatric soft tissue sarcoma samples, enabling molecular reclassification in morphologically ambiguous cases. While the findings support the diagnostic utility of NGS in refining STS diagnosis, the study lacks prospective validation, a comparator arm, and measurement of clinical outcome impact, limiting its strength as evidence for practice change.
Retrospective diagnostic cohort study. Pediatric soft tissue sarcoma patients with 55 tumor samples representing 24 distinct STS subtypes obtained from the Pediatric Oncology Institute biobank (B-053); specific eligibility criteria and clinical demographics not detailed. Intervention: Next-generation sequencing using the Oncomine Childhood Cancer Research Assay (OCCRA) panel to identify molecular alterations. n = 55. Pediatric Oncology Institute - IOP/GRAACC/UNIFESP Biobank; institution located in Brazil (UNIFESP affiliation).
Clinically relevant molecular alterations identified in 70% (37/55) of cases 18 fusion transcripts, 13 SNVs, 8 CNVs, and 6 InDels detected across the cohort Recurrent diagnostic fusions included BCOR::CCNB3, ASPSCR1::TFE3, FUS::DDIT3, EML4::NTRK3, ETV6::NTRK3, CIC::DUX4, NAB2::STAT6, and SS18::SSX1/2
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
NGS-based molecular profiling may enhance diagnostic accuracy in morphologically challenging pediatric soft tissue sarcomas and identify actionable targets for precision therapy; however, clinical utility requires prospective validation showing improved diagnostic concordance and therapeutic outcomes compared to standard histopathology.
Retrospective single-centre biobank study of NGS diagnostic utility in a small, heterogeneous cohort without a prospective validation arm, comparator cohort, or clinical outcome data; demonstrates feasibility and diagnostic reclassification but lacks the rigor needed to claim practice change.
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Quoted from the source exactly as published.
NGS-based molecular profiling may enhance diagnostic accuracy in morphologically challenging pediatric soft tissue sarcomas and identify actionable targets for precision therapy; however, clinical utility requires prospective validation showing improved diagnostic concordance and therapeutic outcomes compared to standard histopathology.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Soft tissue sarcomas (STSs) are a heterogeneous group of rare mesenchymal malignancies with overlapping morphological and immunohistochemical features, often making definitive diagnosis challenging. Recent advances in next-generation sequencing (NGS) have enabled the identification of recurrent molecular alterations that contribute to tumor classification, prognostic stratification, and precision oncology approaches. This retrospective study aimed to evaluate the diagnostic and clinical impact of molecular profiling in pediatric soft tissue sarcomas using the Oncomine Childhood Cancer Research Assay (OCCRA) panel. Fifty-five frozen tumor samples representing 24 distinct soft tissue sarcoma subtypes were obtained from the Pediatric Oncology Institute -IOP/GRAACC/UNIFESP Biobank (B-053). Molecular analysis was performed using NGS to identify gene fusions, single nucleotide variants (SNVs), copy number variations (CNVs), and insertions/deletions (InDels). Clinically relevant molecular alterations were identified in 70% (37/55) of cases, including 18 fusion transcripts, 13 SNVs, 8 CNVs, and 6 InDels. Recurrent and diagnostically relevant alterations included BCOR::CCNB3, ASPSCR1::TFE3, NFR1::BRAF, FUS::DDIT3, EML4::NTRK3, ETV6::NTRK3, CIC::DUX4, NAB2::STAT6 and SS18::SSX1/2 fusions, as well as amplifications involving PDGFRA, FGFR1, GLI1, CDK4, ERBB3, and KIT. Pathogenic variants affecting genes involved in tumor suppression and chromatin remodeling, including TP53, NF1, DICER1, SMARCA4, PTEN, and PIK3CA, were also detected. Importantly, molecular profiling had significant diagnostic impact in several histologically ambiguous tumors, enabling molecular reclassification and refinement of previously inconclusive or inaccurate pathological diagnoses. In multiple cases, NGS transformed descriptive histopathological interpretations into genetically defined sarcoma entities, including NTRK-rearranged spindle cell neoplasms, CIC-rearranged sarcomas, synovial sarcoma, low-grade fibromyxoid sarcoma, and clear cell sarcoma. Furthermore, the identification of actionable alterations highlighted potential opportunities for targeted therapies and precision medicine approaches. Our findings demonstrate that comprehensive molecular profiling significantly enhances diagnostic accuracy in pediatric soft tissue sarcomas, particularly in morphologically challenging cases. The integration of NGS into routine sarcoma diagnostics enables biologically informed tumor classification and supports personalized therapeutic strategies.
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