Project name: SWI/SNF inhibition leads to epigenetic reprogramming in rhabdoid tumor [ATAC-seq]

Description: Rhabdoid tumor is a pediatric cancer characterized by the biallelic inactivation of SMARCB1, a subunit of the SWI/SNF chromatin remodeling complex. SMARCB1 inactivation leads to SWI/SNF redistribution to favor a proliferative dedifferentiated cellular state. Although this deletion is the known oncogenic driver, SWI/SNF therapeutic targeting remains a challenge. Here we show mithramycin and a second-generation analogue EC-8042 are effective in this tumor type. Mithramycin evicts SWI/SNF from chromatin triggering a cellular response characterized by chromatin compartment remodeling and promoter reprogramming. These effects lead to differentiation and marked xenograft tumor regressions in vivo. This study provides a therapeutic candidate for rhabdoid tumor and an approach that may be applicable to the more than 20% of cancers characterized by mutated SWI/SNF.Overall design: Three biological replicates per treatment and time point were sequenced; ATAC libraries were isolated from individual replicates.

Data type: Epigenomics

Sample scope: Multiisolate

Relevance: Medical

Last updated: 2019-09-13