H3K27me3 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the tri-methylation at the 27th lysine residue of the histone H3 protein.

This tri-methylation is associated with the downregulation of nearby genes via the formation of heterochromatic regions.

H3K27me3 (me3) loss by immunohistochemistry (IHC) is a surrogate marker for Posterior Fossa A ependymoma wherein its loss is attributed to overexpression of Cxorf67/EZH2 inhibitory protein (EZHIP), C17orf96, and ATRX loss. Nambirajan et al. aimed to subgroup PF-EPNs using me3 IHC and study correlations of the molecular subgroups with other histone-related proteins, 1q gain, Tenascin C, and outcome. IHC for me3, acetyl-H3K27, H3K27M, ATRX, EZH2, EZHIP, C17orf96, Tenascin-C, and fluorescence in-situ hybridization for chromosome 1q25 locus were performed on an ambispective PF-EPN cohort (2003-2019). H3K27M-mutant gliomas were included for comparison. Among 69 patients, PFA (me3 loss) constituted 64%. EZHIP overexpression and 1q gain were exclusive to PFA seen in 72% and 19%, respectively. Tenascin C was more frequently positive in PFA (p = 0.02). H3K27M expression and ATRX loss were noted in one case of PFA-EPN each. All H3K27M-mutant gliomas (n = 8) and PFA-EPN (n = 1) were EZHIP negative. C17orf96 and acetyl-H3K27 expression did not correlate with me3 loss. H3K27me3 is a robust surrogate for PF-EPN molecular subgrouping. EZHIP overexpression was exclusive to PFA EPNs and was characteristically absent in Diffuse midline glioma H3 K27M-mutants and the rare PFA harboring H3K27M mutations representing mutually exclusive pathways leading to me3 loss 1).

Nambirajan A, Sharma A, Rajeshwari M, Boorgula MT, Doddamani R, Garg A, Suri V, Sarkar C, Sharma MC. EZH2 inhibitory protein (EZHIP/Cxorf67) expression correlates strongly with H3K27me3 loss in posterior fossa ependymomas and is mutually exclusive with H3K27M mutations. Brain Tumor Pathol. 2020 Nov 1. doi: 10.1007/s10014-020-00385-9. Epub ahead of print. Erratum in: Brain Tumor Pathol. 2021 Jan 9;: PMID: 33130928.
  • h3k27me3.txt
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