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PreprintCC BYbioRxiv

Transcriptomic analysis reveals differential regulation of synaptic components in pediatric and adult brain tumors

  1. 1Seattle Children's; University of Washington School of Medicine; Fred Hutchinson Cancer Center

Abstract

Neuronal-cancer cell interactions are a key component of brain tumor pathophysiology, yet many fundamental questions remain unanswered, with even more remaining unasked. Here, we present a comprehensive brain tumor reference map generated from bulk RNA-seq data of ~4,300 adult and pediatric brain tumors, including various glioma subtypes, medulloblastomas, ependymomas, and meningiomas, alongside ~1,400 healthy brain samples. By analyzing synaptic processes and synaptic gene expression across tumor types, we reveal the complexity of neuron-tumor crosstalk and its potential impact on patient survival. Our findings identify key synaptic signaling pathways and dysregulated patterns in brain tumors, including HNRNPH2 upregulation, a key factor in RNA processing and metabolism, in gliomas and medulloblastomas. Additionally, we highlight the role of cholinergic signaling, particularly CHRNA9, as a driver of glioma progression, which is also upregulated in WNT and Group 4 medulloblastomas, ependymomas, and meningiomas. Furthermore, P2 purinergic signaling emerges as a key player in glioma progression. These insights lay the groundwork for future studies exploring whether targeting these pathways could reprogram the tumor microenvironment toward an anti-tumor state, ultimately leading to novel therapeutic strategies and improved patient outcomes.

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BibTeX
@misc{merinogalan2026transcriptomic,
  title = {{Transcriptomic analysis reveals differential regulation of synaptic components in pediatric and adult brain tumors}},
  author = {L. Merino-Galan and S. Arora and G. Glatzer and M. Jensen and A. Rajendran and E. C. Holland and S. S. Pattwell},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.30.755821},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.30.755821v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Transcriptomic analysis reveals differential regulation of synaptic components in pediatric and adult brain tumors
AU  - L. Merino-Galan
AU  - S. Arora
AU  - G. Glatzer
AU  - M. Jensen
AU  - A. Rajendran
AU  - E. C. Holland
AU  - S. S. Pattwell
PY  - 2026
DA  - 2026/09/30
PB  - bioRxiv
DO  - 10.64898/2026.09.30.755821
UR  - https://www.biorxiv.org/content/10.64898/2026.09.30.755821v1
AB  - Neuronal-cancer cell interactions are a key component of brain tumor pathophysiology, yet many fundamental questions remain unanswered, with even more remaining unasked. Here, we present a comprehensive brain tumor reference map generated from bulk RNA-seq data of ~4,300 adult and pediatric brain tumors, including various glioma subtypes, medulloblastomas, ependymomas, and meningiomas, alongside ~1,400 healthy brain samples. By analyzing synaptic processes and synaptic gene expression across tumor types, we reveal the complexity of neuron-tumor crosstalk and its potential impact on patient survival. Our findings identify key synaptic signaling pathways and dysregulated patterns in brain tumors, including HNRNPH2 upregulation, a key factor in RNA processing and metabolism, in gliomas and medulloblastomas. Additionally, we highlight the role of cholinergic signaling, particularly CHRNA9, as a driver of glioma progression, which is also upregulated in WNT and Group 4 medulloblastomas, ependymomas, and meningiomas. Furthermore, P2 purinergic signaling emerges as a key player in glioma progression. These insights lay the groundwork for future studies exploring whether targeting these pathways could reprogram the tumor microenvironment toward an anti-tumor state, ultimately leading to novel therapeutic strategies and improved patient outcomes.
ER  -