TMIC-71. SPATIAL ANALYSIS OF GENETIC HETEROGENEITY AND TUMOR MICROENVIRONMENT INTERACTIONS IN GLIOBLASTOMA

Abstract Genetic variation can be considered a driver of somatic evolution in glioblastoma (GBM); however, the tumor microenvironment (TME) is key contributor to selection process and evolutionary potential cancer cells. Although diverse ecosystems exist GBM which impact cell fitness characterize an aggressive pathophysiology, little known about how genetically distinct subpopulations cells interact with surrounding TME. Therefore, we sought investigate varying clonal genotypes are influenced by different types selective pressures within Our imaging-based strategy centered around Specific-to-Allele PCR Florescence In Situ Hybridization (STAR-FISH), situ based probe hybridization method for detection point mutations copy number variations at single-cell level. Using STAR-FISH illuminate spatial distribution clones TERT promoter, integrated multicolor immunofluorescent staining, DNA-FISH, reflectance imaging, computational cellular analysis methods achieve highly-multiplexed single profiling intact specimens. With this able simultaneously evaluate tissues presence hypoxic, angiogenic, inflammatory niches, extracellular matrix organization, nuclear morphology, mutational status, several oncogenic amplifications on same slide location. We analyzed 20 matched primary recurrent samples, imaging regions tumor. initial results have revealed interesting potentially novel distributions subclones residing specific microenvironments. These include mutation positive enriched areas possessing more structured matrix, as well unique arrangements infiltrating immune angiogenic niche. This research underscores importance TME selecting certain phenotypes that evolution, highlighting genetic dependencies sustain heterogeneity GBM.