Transcriptional changes mediated by the HDACi belinostat in IDH-mutant glioma cultures with YAP and TAZ overexpression

IDH1/2 mutations (IDHmut) increase methylation of DNA and histones in gliomas. IDHmut inhibitors are effective against low-grade IDHmut gliomas, but new strategies against high grade IDHmut gliomas are needed. Although histone deacetylase inhibitors (HDACi) are ineffective against IDHwt glioblastoma (GBM), their potential in IDHmut gliomas has not been extensively studied. We previously established that IDHmut gliomas are more sensitive to HDACi than IDHwt GBM. Here we show that IDHmut is associated with greater sensitivity to HDACi only in glioma, not in IDHmut chondrosarcoma or cholangiocarcinoma. Two mediators of HDACi resistance, YAP and TAZ, were methylated and suppressed in IDHmut gliomas, but not in other IDHmut cancers. Inducing YAP or TAZ expression in IDHmut gliomas conferred resistance to HDACi. Here, we report the transcriptional changes mediated by the HDACi belinostat in IDHmut glioma with and without YAP or TAZ expression. RNA seq profiling of belinostat-treated 0905 and TS603 IDH mutant glioma cultures, with and without YAP 5SA and TAZ 4SA expression.