CSIG-24. EPIGENETIC SUPPRESSION ALLOWS GBM TO MAINTAIN P53 WILD-TYPE STATUS

Abstract Introduction Glioblastoma (GBM) is the most common primary brain malignancy in adults. The vast majority of GBM cases maintain wild-type status p53, protein considered to be critical tumor suppressor. How displays such a malignant phenotype despite retaining normal p53 unknown. We also aim translate these molecular findings into therapeutics via randomized clinical trial. METHODS A variety biological techniques were employed. These include CRISPR-CAS, next generation sequencing, stereotactic mouse injections, and histological analyses human tumors. Approval for small, single site, blinded, trial newly diagnosed underway. Overall survival, recurrence-free immunohistochemical will assessed. RESULTS Human cell lines express Brd at higher levels compared mutant (~10 fold, p < 0.05). Cell viability assays show that deletion leads ~50% decrease (p 0.05) survival. Critically, this effect abrogated upon itself, showing functions through inhibition p53’s suppressive effects. Furthermore, immunoprecipitation shows it member complex proteins bind target genes. importance are corroborated vivo, as mice stereotactically injected with cells lack survive ~2-fold longer than retain Brd. have begun process start trials an already FDA-approved drug (currently used treatment lymphoma sarcoma) blocks pathway. CONCLUSION key suppressor genes GBM. binds multimeric complex, which inhibits Thus, effects prevented Inhibition pathway patients