Targeting the Clear Cell Sarcoma Oncogenic Driver Fusion Gene EWSR1::ATF1 by HDAC Inhibition.

ABSTRACT: Clear cell sarcoma (CCS), a rare but extremely aggressive malignancy with no effective therapy, is characterized by the expression of the oncogenic driver fusion gene EWSR1::ATF1. In this study, we performed a high-throughput drug screening, finding that the histone deacetylase inhibitor vorinostat exerted an antiproliferation effect with the reduced expression of EWSR1::ATF1. We expected the reduced expression of EWSR1::ATF1 to be due to the alteration of chromatin accessibility; however, assay for transposase-accessible chromatin using sequencing and a cleavage under targets and release using nuclease assay revealed that chromatin structure was only slightly altered, despite histone deacetylation at the EWSR1::ATF1 promoter region. Alternatively, we found that vorino

SUBMITTER: Mae H 

PROVIDER: S-EPMC10317042 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature