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Annual Review of Cancer Biology

Volume 6, 2022

Oncohistones: Hijacking the Histone Code

Abstract

Chromatin dysfunction has been implicated in a growing number of cancers especially in children and young adults. In addition to chromatin-modifying and -remodeling enzymes, mutations in histone genes are linked to human cancers. Since the first reports of hotspot missense mutations affecting key residues at the histone H3 tail, studies have revealed how these so-called oncohistones dominantly (H3K27M and H3K36M) or locally (H3.3G34R/W) inhibit corresponding histone methyltransferases and misregulate epigenome and transcriptome to promote tumorigenesis. More recently, widespread mutations in all four core histones are identified in diverse cancer types. Furthermore, an oncohistone-like protein EZHIP has been implicated in driving childhood ependymomas through a mechanism highly reminiscent of H3K27M mutation. Here we review recent progress in understanding the biochemical, molecular, and biological mechanisms underlying the canonical and novel histone mutations. Importantly, these mechanistic insights have identified therapeutic opportunities for oncohistone-driven tumors.

Keyword(s): cancer epigenetics, chromatin, EZHIP, histone methylation, histone mutations, oncohistones
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/content/journals/10.1146/annurev-cancerbio-070120-102521
2022-04-11
2024-04-24
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/content/journals/10.1146/annurev-cancerbio-070120-102521
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Oncohistones: Hijacking the Histone Code
Annual Review of Cancer Biology 6, 293 (2022); https://doi.org/10.1146/annurev-cancerbio-070120-102521
/content/journals/10.1146/annurev-cancerbio-070120-102521
/content/journals/10.1146/annurev-cancerbio-070120-102521
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  • Article Type: Review Article

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