HGG-31. GENOMIC CORRELATIONS WITH HEMORRHAGE RISK IN PEDIATRIC PATIENTS WITH DIFFUSE HEMISPHERIC GLIOMA

Abstract

Abstract BACKGROUND Pediatric diffuse hemispheric glioma (DHG) is a histone-mutated (H3.3G34R/V) high-grade glioma with poor prognosis. Clinical observation and previous reports have identified that a subset of patients present with tumor-associated hemorrhage. Here, we present our findings from radiological review of these patients and determine genomic risk factors predictive for hemorrhage risk in this cohort. METHODS Data was abstracted through the Children’s Brain Tumor Network (CBTN) and EGAS00001004301. Transcriptomic and genomic analyses were completed in R 4.3.1 using edgeR, msigdbr, and xCell. Presence of blood products was determined on preoperative MRI by a board certified pediatric neuroradiologist. RESULTS 48 samples were available across cohorts with transcriptomic or genomic data. 10 samples (21%) had pre-operative imaging and transcriptomic data available. Initial analysis determined that 6 samples (60%) had acute/chronic hemorrhage based on radiological review. Samples with hemorrhage had increased levels of VEGFA (LFC: 3.45, p=2E-07) and CA9 (LFC: 5.97, p=8E-05) expression on the transcriptomic level suggesting that patients with high expression of these markers (AngioHi) had increased risk of hemorrhage compared to patients with low expression of these markers (AngioLo). AngioHi patients had notably higher levels of IL8 (LFC: 3.56, p=0.01) and increased macrophage populations. Genomic information was available for 15 samples (31%, 7 AngioHi, 8 AngioLo). PTEN alterations (n=4, 57%), FBXW7 alterations (n= 2, 29%), or PDGFRa driver alterations (n= 3, 43%) were found in the AngioHi cohort while none of these alterations were identified in the AngioLo cohort. Notably, at least one of these mutations was seen in all cases in the AngioHi cohort. CONCLUSIONS These findings identify potential mutational alterations predictive for tumor-associated hemorrhage in pediatric DHG. Current work is being completed to further characterize how these mutations impact vascular remodeling for patients with DHG and may offer targeted therapeutic opportunities.