Afraah Cassim, Matthew D Dun, David Gallego-Ortega, Fatima Valdes-Mora
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EZHIP's role in diffuse midline glioma: echoes of oncohistones?
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.
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Trends in Cancer, a part of the Trends review journals, delivers concise and engaging expert commentary on key research topics and cutting-edge advances in cancer discovery and medicine.
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