biostudies-literatureMae HMEXT | Japan Society for the Promotion of ScienceOsaka Medical Research Foundation for Intractable Diseases1152-1165https://www.ebi.ac.uk/biostudies/studies/S-EPMC10317042biostudies-literatureUnknown3(7)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 <i>EWSR1::ATF1</i>. 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 <i>EWSR1::ATF1</i>. We expected the reduced expression of <i>EWSR1::ATF1</i> 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 vorinoCancer research communicationsTargeting the Clear Cell Sarcoma Oncogenic Driver Fusion Gene <i>EWSR1::ATF1</i> by HDAC Inhibition.PMC10317042JP22K09375JP22K16766JP19K18481JP19K18498Mae HOutani HImura YYasuda NInoue ANakai TTakenaka SChijimatsu RKotani YOkada SNakai SfalseTargeting the Clear Cell Sarcoma Oncogenic Driver Fusion Gene <i>EWSR1::ATF1</i> by HDAC Inhibition.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 <i>EWSR1::ATF1</i>. 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 <i>EWSR1::ATF1</i>. We expected the reduced expression of <i>EWSR1::ATF1</i> 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 vorino2023-01-01T00:00:00Z2023 Jul2026-05-29T09:06:11.574Z2025-02-19T03:21:21.614ZS-EPMC103170423740512310.1158/2767-9764.CRC-22-0518