Transcriptional changes mediated by the HDACi panobinostat in IDH-wildtype and IDH-mutant gliomas
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 unique transcriptional changes mediated by the HDACi panobinostat in glioma, providing insight into the mecahnism of increased HDACi sensitivithy.. Overall design: IDH1/2 wildtype glioma cultures (0827, 0923, 0211, GBM12, GBM43) and IDH1/2 mutant (0905, BT142, TS603, TB09) were treatred with 10 nM panobinostat and evaluated for unique transcriptional signatures that would indicate why IDH1/2 mutant gliomas are more sensitive to HDACi