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<p>Sarcomas are rare, heterogeneous mesenchymal malignancies with notably high misdiagnosis rates. Despite sarcoma patients in China representing about one-quarter of the global disease burden, large-scale NGS-based diagnostic studies remain scarce, with limited sample sizes failing to capture the extensive subtype complexity of sarcomas. To address diagnostic gaps, we conducted the largest multicenter study in China involving 788 patients with soft tissue or bone sarcomas. All samples underwent targeted RNA sequencing (Fusioncapture) alongside standard histopathology, immunohistochemistry, and DNA-based next-generation sequencing (NGS). Compared with DNA-NGS, RNA-based profiling clarified ambiguous fusion calls and uncovered numerous additional and clinically relevant events, including 281 fusions not captured by the DNA panel. Notably, 114 recurrent alterations were strongly subtype-associated, and 20 newly identified receptor tyrosine kinase fusions had therapeutic significance, expanding targetable cases from 3.3% to 6.5%. Furthermore, integrated RNA data led to subtype reclassification in 11.9% of patients, including 22% of those initially diagnosed as “not otherwise specified”. These findings confirm the utility of targeted RNA sequencing for detecting transcriptionally active fusions, refining pathological classifications, and identifying actionable variants in Chinese sarcoma patients. Despite retrospective design and limited orthogonal validation of some fusions, our results strongly support incorporating RNA-based assays into routine clinical workflows. Ultimately, this integrated approach can improve diagnostic precision, guide personalized treatment strategies, and enhance outcomes for sarcoma patients.</p>

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Superiority of targeted RNA sequencing for fusion detection and subtype diagnosis in Chinese sarcoma patients: a multicenter study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月14日

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  • Gu Jin,
  • Dandan Zhao,
  • Baoming Wang,
  • Xuejiao Liu,
  • Quanyu Yang,
  • Zhengchuang Liu,
  • Qiong Yang,
  • Jianhua Zhu,
  • Jie Zhang,
  • Wei Li,
  • Xiaojuan Wang,
  • Chunyang Wang,
  • Tonghui Ma,
  • Jiayong Liu

摘要

Sarcomas are rare, heterogeneous mesenchymal malignancies with notably high misdiagnosis rates. Despite sarcoma patients in China representing about one-quarter of the global disease burden, large-scale NGS-based diagnostic studies remain scarce, with limited sample sizes failing to capture the extensive subtype complexity of sarcomas. To address diagnostic gaps, we conducted the largest multicenter study in China involving 788 patients with soft tissue or bone sarcomas. All samples underwent targeted RNA sequencing (Fusioncapture) alongside standard histopathology, immunohistochemistry, and DNA-based next-generation sequencing (NGS). Compared with DNA-NGS, RNA-based profiling clarified ambiguous fusion calls and uncovered numerous additional and clinically relevant events, including 281 fusions not captured by the DNA panel. Notably, 114 recurrent alterations were strongly subtype-associated, and 20 newly identified receptor tyrosine kinase fusions had therapeutic significance, expanding targetable cases from 3.3% to 6.5%. Furthermore, integrated RNA data led to subtype reclassification in 11.9% of patients, including 22% of those initially diagnosed as “not otherwise specified”. These findings confirm the utility of targeted RNA sequencing for detecting transcriptionally active fusions, refining pathological classifications, and identifying actionable variants in Chinese sarcoma patients. Despite retrospective design and limited orthogonal validation of some fusions, our results strongly support incorporating RNA-based assays into routine clinical workflows. Ultimately, this integrated approach can improve diagnostic precision, guide personalized treatment strategies, and enhance outcomes for sarcoma patients.