Furthermore, we show that, in the context of retained histone H3 lysine 27 trimethylation (H3K27me3), I ACVR1 i -mutant PF ependymomas exhibit a DNA methylation signature distinct from other PF ependymomas. I TERT i promoter mutations combined with monosomy of chromosome 6 were recently shown to identify a group of clinically aggressive posterior fossa ependymal tumors with hybrid histologic and epigenetic features of ependymoma and subependymoma (EPN/SE) [[13]]. Here, we show that posterior fossa ependymomas harboring I ACVR1 i mutation with retained H3K27me3 have overlapping clinicopathologic features with PFB ependymomas but resolve into a unique epigenetic subgroup distinct from other currently recognized ependymoma/subependymoma DNA methylation classes. In contrast to I ACVR1 i -mutant DMG, I ACVR1 i -mutant PF ependymomas lacked histone H3 mutation and co-occurring alterations in I PIK3CA i , I PIK3R1 i , and I PPM1D i (Fig. [Extracted from the article]