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<p>Solitary fibrous tumors (SFTs) of the central nervous system (CNS) are rare, aggressive mesenchymal neoplasms with high recurrence and metastasis rates. Here, we perform a comprehensive multi-omics analysis of 189 cases of CNS SFTs integrating 94 whole genome sequencing, 88 transcriptomics, 7 single-nucleus RNA sequencing and 3 spatial transcriptome sequencing. We find that receptor tyrosine kinase mutations are significantly more prevalent besides the widespread <i>NAB2-STAT6</i> fusion and correlate with tumor grade. Transcriptomic analysis reveals four molecular subtypes—classical, neural-like, inflamed and migratory—each associated with distinct clinical and biological characteristics. Single-nucleus RNA sequencing identifies five tumor cell states, with the SFT_classical state serving as a precursor to other states influenced by hypoxia and inflammation. Notably, we identify FER kinase as a key therapeutic target, with FER inhibition significantly reducing tumor cell proliferation, migration and invasion. These findings provide important insights into CNS SFT biology and suggest potential therapeutic strategies for this challenging tumor type.</p>

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Molecular landscape, subtypes, and therapeutic vulnerabilities of central nervous system solitary fibrous tumors

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月23日

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  • Chenhui Zhao,
  • Xueyan Hu,
  • Xiudong Guan,
  • Xiaojun Fu,
  • Tingting Wang,
  • Mengyuan Li,
  • Xinze Liu,
  • Jiarui Zhao,
  • Di Wu,
  • Fan Zhang,
  • Jiaying Fu,
  • Jiang Li,
  • Tieqiang Zhang,
  • Xiaochun Jiang,
  • Changxiang Yan,
  • Wang Jia,
  • Ence Yang,
  • Jian Chen

摘要

Solitary fibrous tumors (SFTs) of the central nervous system (CNS) are rare, aggressive mesenchymal neoplasms with high recurrence and metastasis rates. Here, we perform a comprehensive multi-omics analysis of 189 cases of CNS SFTs integrating 94 whole genome sequencing, 88 transcriptomics, 7 single-nucleus RNA sequencing and 3 spatial transcriptome sequencing. We find that receptor tyrosine kinase mutations are significantly more prevalent besides the widespread NAB2-STAT6 fusion and correlate with tumor grade. Transcriptomic analysis reveals four molecular subtypes—classical, neural-like, inflamed and migratory—each associated with distinct clinical and biological characteristics. Single-nucleus RNA sequencing identifies five tumor cell states, with the SFT_classical state serving as a precursor to other states influenced by hypoxia and inflammation. Notably, we identify FER kinase as a key therapeutic target, with FER inhibition significantly reducing tumor cell proliferation, migration and invasion. These findings provide important insights into CNS SFT biology and suggest potential therapeutic strategies for this challenging tumor type.