Transcriptomic Portraits and Molecular Pathway Activation Features of Adult Spinal Intramedullary Astrocytomas

In this study, we report 31 spinal intramedullary astrocytoma (SIA) RNA sequencing (RNA-seq) profiles for 25 adult patients with documented clinical annotations. To our knowledge, this is the first clinically annotated RNA-seq dataset of spinal astrocytomas derived from the intradural intramedullary compartment. We compared these tumor profiles with the previous healthy central nervous system (CNS) RNA-seq data for spinal cord and brain and identified SIA-specific gene sets and molecular pathways. Our findings suggest a trend for SIA-upregulated pathways governing interactions with the immune cells and downregulated pathways for the neuronal functioning in the context of normal CNS activity. In two patient tumor biosamples, we identified diagnostic KIAA1549-BRAF fusion oncogenes, and we also found 16 new SIA-associated fusion transcripts. In addition, we bioinformatically simulated activities of targeted cancer drugs in SIA samples and predicted that several tyrosine kinase inhibitory drugs and thalidomide analogs could be potentially effective as second-line treatment agents to aid in the prevention of SIA recurrence and progression.

Automated summary

This study analyzed 31 spinal intramedullary astrocytoma samples using RNA sequencing and identified specific gene expression pathways involved in immune cell interactions and neuronal functioning in SIA. The study also discovered new fusion transcripts associated with SIA and predicted potential effectiveness of certain targeted cancer drugs in SIA treatment.