Abstract Body: Introduction: Vein of Galen malformations (VOGM) are embryonic choroid plexus-derived arteriovenous malformations which may develop secondary to mosaicism. Sequencing of peripheral whole blood is often ineffective in identifying novel mutations responsible for VOGM development. Whole blood is typically considered to be a transcriptionally homogenous tissue, although vascular microenvironments may impart site-specific transcriptional changes. Here, we investigated whether peripherally collected whole blood samples would yield a different transcriptomic signature compared to targeted blood collection near a biologically active lesion.

Methods: Whole blood was prospectively collected from femoral access (peripheral) and catheterized intracranial feeding vessels (intralesional) during endovascular embolization of 8 patients for management of VOGM. All blood samples were matched and collected within the same endovascular procedure. RNA sequencing of 15,730 genes from 23 samples after quality-control was aligned, normalized, and residualized using Rsubread, sva, and limma/voom. Differentially expressed genes (DEGs) were identified between peripheral and intralesional blood draws. Gene set enrichment analysis (GSEA) was conducted using Gene Ontology biological processes and cellular components.

Results: 430 genes (196 upregulated, 234 downregulated) were differentially expressed in whole blood collected from intracranial feeders to the VOGM versus the femoral artery. When comparing matched samples, tissue-specific choroid plexus and VOGM-associated genes were significantly upregulated in intralesional whole blood. This included IQUB, a gene involved in ciliary formation and function, expressed at high degrees in the brain in the ventricular ependyma and choroid plexus; UBXN10, a cilium assembly gene which demonstrates body-wide tissue specificity for the choroid plexus; and PTGIS, a nonspecific prostacyclin synthase secreted by neovessels developing in the context of CNS inflammation.

Conclusion: We demonstrate the first evidence of differential whole blood transcriptomic signatures by anatomical location. Intracranially collected whole blood of VOGM patients demonstrated upregulation of choroid plexus-specific genes compared to femoral arterial blood collected during the same procedure. Future studies assessing peripheral whole blood transcriptomes should consider the added prognostic value of targeted endovascular blood draws for cell-free molecular profiling.