2. Academic Validation
  3. Molecular landscape, subtypes, and therapeutic vulnerabilities of central nervous system solitary fibrous tumors

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

  • Nat Commun. 2025 Aug 23;16(1):7870. doi: 10.1038/s41467-025-63039-4.
Chenhui Zhao # 1 2 3,  Xueyan Hu # 4,  Xiudong Guan # 5 6 7,  Xiaojun Fu # 8,  Tingting Wang # 1 2 9,  Mengyuan Li 1 2 9,  Xinze Liu 1 2,  Jiarui Zhao 1 2 9,  Di Wu 1 2 10,  Fan Zhang 11,  Jiaying Fu 1 2,  Jiang Li 5 6 7,  Tieqiang Zhang 5 6 7,  Xiaochun Jiang 12,  Changxiang Yan 13,  Wang Jia 14 15 16,  Ence Yang 17,  Jian Chen 18 19 20
Affiliations

Affiliations

  • 1 Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 102206, China.
  • 2 Chinese Institute for Brain Research, Beijing, Beijing, 102206, China.
  • 3 Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, China.
  • 4 Department of Medical Bioinformatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
  • 5 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
  • 6 China National Clinical Research Center for Neurological Diseases (NCRC-ND), Beijing, 100070, China.
  • 7 National Center for Neurological Disorders, Beijing, 100070, China.
  • 8 Department of Neurosurgery, Sanbo Brain Hospital Capital Medical University; No. 50, Yikesong Road, Xiangshan, Haidian District, Beijing, 100193, People's Republic of China.
  • 9 Changping Laboratory, Beijing, 102206, China.
  • 10 School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
  • 11 Department of Pathology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, China.
  • 12 Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, China. jiangxiaochun@wnmc.edu.cn.
  • 13 Department of Neurosurgery, Sanbo Brain Hospital Capital Medical University; No. 50, Yikesong Road, Xiangshan, Haidian District, Beijing, 100193, People's Republic of China. yancx65828@163.com.
  • 14 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China. jwttyy@126.com.
  • 15 China National Clinical Research Center for Neurological Diseases (NCRC-ND), Beijing, 100070, China. jwttyy@126.com.
  • 16 National Center for Neurological Disorders, Beijing, 100070, China. jwttyy@126.com.
  • 17 Department of Medical Bioinformatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. yangence@pku.edu.cn.
  • 18 Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 102206, China. chenjian@cibr.ac.cn.
  • 19 Chinese Institute for Brain Research, Beijing, Beijing, 102206, China. chenjian@cibr.ac.cn.
  • 20 Changping Laboratory, Beijing, 102206, China. chenjian@cibr.ac.cn.
  • # Contributed equally.
PMID: 40849425 DOI: 10.1038/s41467-025-63039-4
Abstract

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.

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