Cassim Afraah, Dun Matthew D, Gallego-Ortega David, Valdes-Mora Fatima
Cancer Epigenetic Biology and Therapeutics Laboratory, Children's Cancer Institute, Lowy Cancer Centre, Kensington, New South Wales, Australia; School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, New South Wales, Australia.
Cancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine, and Wellbeing, University of Newcastle, Callaghan, New South Wales, Australia; Precision Medicine Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia; Paediatric Stream, Mark Hughes Foundation Centre for Brain Cancer Research, College of Health, Medicine, and Wellbeing, Callaghan, New South Wales, Australia.
Trends Cancer. 2024 Dec;10(12):1095-1105. doi: 10.1016/j.trecan.2024.09.002. Epub 2024 Sep 28.
The enhancer of zeste inhibitory protein (EZHIP) is typically expressed during germ cell development and has been classified as a cancer-testis antigen (CTA) in various cancers. In 2020, 4% of diffuse midline gliomas (DMGs) were shown to aberrantly express EZHIP, mirroring the DMG hallmark histone H3 K27M (H3K27M) oncohistone mutation. Similar to H3K27M, EZHIP is a negative regulator of polycomb repressive complex 2 (PRC2), leading to global epigenomic remodeling. In this opinion, we explore the similarities and disparities between H3K27M- and EZHIP-DMGs with a focus on their shared functional hallmark of PRC2 inhibition, their genetic and epigenomic landscapes, plausible differences in the cell of origin, and therapeutic avenues. Upcoming research on EZHIP will help better understand its role in gliomagenesis and DMG therapy.
zeste抑制蛋白增强子（EZHIP）通常在生殖细胞发育过程中表达，并在多种癌症中被归类为癌胚抗原（CTA）。2020年研究表明，4%的弥漫性中线胶质瘤（DMG）异常表达EZHIP，这与DMG标志性的组蛋白H3 K27M（H3K27M）癌组蛋白突变情况相似。与H3K27M类似，EZHIP是多梳抑制复合物2（PRC2）的负调节因子，可导致整体表观基因组重塑。在本观点文章中，我们探讨了H3K27M和EZHIP相关DMG之间的异同，重点关注它们共同的PRC2抑制功能特征、遗传和表观基因组格局、可能存在的细胞起源差异以及治疗途径。关于EZHIP的后续研究将有助于更好地了解其在胶质瘤发生和DMG治疗中的作用。
