Changes in Histone H3 acetylation in panobinostat-treated IDH-wildtype and IDH-mutant glioma cultures

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 in glioma. While HDACi induced more histone acetylation and gene regulation in IDHmut glioma than in IDHwt GBM, ChIP-Seq studies show such acetylation was mostly within gene deserts, whereas IDHmut glioma promoters paradoxically lost histone acetylation.