EPCO-43. CHROMATIN REMODELERS LOST IN TRANSLATION

Abstract The chromatin remodeler complexes mammalian SWI/SNF (SWItch/Sucrose Non-Fermentable) are altered in more than 40% of cancers and involved therapeutic resistance. In children,SMARCB1 is mutated 95% rhabdoid tumors, the remaining 5% present mutations SMARCA4. These tumors typically identified children younger three years old have a very poor prognosis with survival under one year following diagnosis. SMARCB1 expression also lost 90% epithelial sarcomas, rare aggressive tumor affecting young adults, 50% pediatric chordomas. Additional mSWI/SNF subunits highly childhood such as ARID1A ARID1B neuroblastomas, most common solid children, ARID SMARCA4 medulloblastomas, brain cancer children. To date, roles normal cells still largely undetermined focus on nuclear functions. However, our assessment genetic dependencies drug sensitivity screens revealed that for genetically dependent exclusively sensitive to translation factors pathway inhibitors. We demonstrate extensively localized cytoplasm they interact initiation machinery. Furthermore, short-term inhibition, depletion specific alter protein synthesis increase Most these being considered loss function, results suggest potential opportunity diseases presenting complexes. conclusion, work demonstrates remodelers direct will not only be relevant molecular understanding but lead new opportunities.