EPCO-17. UNMASKING CLONAL EVOLUTION OF DIFFUSE INTRINSIC GLIOMA USING MULTI-MODAL GENOMIC DATA

Abstract Diffuse intrinsic pontine glioma (DIPG) is an infiltrative incurable tumor affecting children. DIPG tumors often harbor a recurrent H3K27M mutation which leads to global loss of H3K27me2/3 and overall DNA hypomethylation, suggesting important role the epigenome, consequent transcriptome in pathogenesis. To thoroughly characterize clonal evolution DIPG, we collected 33 samples from 7 patients using multi-region sampling strategy generated whole-exome sequencing, methylation profiling data. Using our novel bioinformatics approach, 28 distinct sub-clones were identified characterized cohort whilst simultaneously interrogating tumor’s ability migrate disseminate. When present, initiating clone (Clone 1) exclusively contained with significant changes whereas divergent clones that arise later evolutionary trees typically driven by copy number aberrations. Further characterization unique gene expression profiles (i.e. cell migration angiogenesis programs) support enable dissemination. In this study, uncovered how evolves at genetic, epigenetic, transcriptional levels parallel doing so, reveal phenotypes sub-clonal level related behavior. We are further validating these results single-cell RNA sequencing experiments gaining insights into underlying molecular mechanisms responsible for invasive aggressive phenotypes.