Next-Generation Sequencing Refines Diagnosis and Expands Precision Medicine Opportunities in Soft Tissue Sarcomas

Sep 22, 2026

Soft tissue sarcomas are a heterogeneous group of rare mesenchymal malignancies whose overlapping morphology and immunohistochemistry can hinder definitive diagnosis. A retrospective study assessed the diagnostic and clinical impact of molecular profiling in pediatric soft tissue sarcomas using the Oncomine Childhood Cancer Research Assay panel. Fifty-five frozen samples across 24 subtypes were analyzed by next-generation sequencing, detecting clinically relevant alterations in 70% of cases, supporting molecular reclassification and precision oncology opportunities.

LanguageEnglish

CategoryHealthcare

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Pages17

Reading Time43 min

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Abstract

1. Introduction

Article Next-Generation Sequencing Refines Diagnosis and Expands Precision Medicine Opportunities in Soft Tissue Sarcomas Francine Tesser-Gamba 1,2, *, Thais Biude Mendes 1, Fernanda Teresa Lima 1,3, Simone de Campos Vieira Abib 4, Eliana Maria Monteiro Caran 5 and Silvia Regina Caminada de Toledo 1,2 Academic Editors: Adam Szpechci ´nski and Magdalena Pelc Received: 11 June 2026 Revised: 3 August 2026 Accepted: 5 August 2026 Published: 12 August 2026 Copyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Genetics Laboratory, Pediatric Oncology Institute (IOP/GRAACC), Federal University of Sao Paulo, Sao Paulo 04039-001, SP, Brazil 2 National Science and Technology Institute for Children’s Cancer Biology and Pediatric Oncology—INCT BioOncoPed, Porto Alegre 90010-150, RS, Brazil 3 Department of Gynecology, Federal University of Sao Paulo, Sao Paulo 04024-002, SP, Brazil 4 Department of Pediatric Surgery, Pediatric Oncology Institute (IOP/GRAACC), Federal University of Sao Paulo, Sao Paulo 04023-062, SP, Brazil; [simoneabib@uol.com.br](simoneabib@uol.com.br) 5 Department of Pediatrics Pediatric Oncology Institute (IOP/GRAACC), Federal University of Sao Paulo, Sao Paulo 04023-062, SP, Brazil * Correspondence: [francinegamba@graacc.org.br](francinegamba@graacc.org.br); Tel.: +55-11-5080-8582 Abstract 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 NTRKrearranged 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 classificatio

FAQs

What is the main purpose of the study described in the article?

To evaluate how molecular profiling using a next-generation sequencing panel affects diagnosis and clinical outcomes in pediatric soft tissue sarcomas.

How were molecular alterations detected in the patient samples?

The study used next-generation sequencing with the Oncomine Childhood Cancer Research Assay (OCCRA) panel to identify gene fusions, SNVs, CNVs, and insertions/deletions.

What diagnostic impact did molecular profiling have in morphologically ambiguous tumors?

It enabled molecular reclassification, refining previously inconclusive or inaccurate pathological diagnoses and converting descriptive histopathology into genetically defined sarcoma entities.

Sep 22, 2026

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