IMG-07. MOLECULAR PROCESSES GIVE RISE TO EMERGENCE OF RADIO-PHENOTYPES ON MRI SCANS OF PEDIATRIC LOW-GRADE GLIOMA

Abstract There is mounting evidence that tumor microenvironmental pressure selects for somatic genetic alterations contribute to the formation of distinct morphological characteristics, captured on radiology scans as radio-phenotypes. Such phenotypic variations are a source heterogeneity in clinical manifestation tumors same histology across patients, and part, their heterogeneous responses therapies. Deeper understanding associations between genotype radio-phenotype pediatric low-grade glioma (pLGG), most histologically diverse childhood brain tumor, may facilitate precision diagnostic therapeutic approaches. Here, we categorize pLGGs into relatively homogeneous imaging subtypes based radiomic features further explore these with genotype. From multiparametric MRI 167 from Children’s Brain Tumor Network (CBTN), 881 variables (tumor location, age, gender) were extracted. After dimensionality reduction using principal component analysis (PCA), K-Means clustering was applied 19 components group patients three subtypes. Using whole transcriptomic data OpenTargets, differential expression co-expression network- pathway-level immune-related signaling compared among Gene Set Enrichment Analysis (GSEA) revealed differentially higher cell cycle regulatory, extracellular matrix (ECM) remodeling, migratory pathways subtype1 than 2 3, upregulation ECM 1 subtype3. Based Sets Net Correlations (GSNCA), exhibited co-regulation TNF/TNFR1 subtype2, RHOG GTPase TGFB1pathways when against Subtype2 showed NOTCH1 transcriptional regulatory pathways. Our proposed multi-disciplinary radiomic-genomic approach elucidates molecular biological processes associated emergence pLGG.