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Updated: May 6, 2026

Author Spotlight: Epigenetic Modifications and Metabolic Rewiring as Targets for Cancer Therapy
Published on: October 18, 2024
Histone H3.3 mutations: a variant path to cancer
Benjamin T K Yuen1, Paul S Knoepfler
1Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, 4303 Tupper Hall, Davis, CA 95616, USA; Genome Center, University of California Davis School of Medicine, 451 Health Sciences Drive, Davis, CA 95616, USA; Institute of Pediatric Regenerative Medicine, Shriners Hospital For Children Northern California, 2425 Stockton Boulevard, Sacramento, CA 95817, USA.
Abstract:
A host of cancer types exhibit aberrant histone modifications. Recently, distinct and recurrent mutations in a specific histone variant, histone H3.3, have been implicated in a high proportion of malignant pediatric brain cancers. The presence of mutant H3.3 histone disrupts epigenetic posttranslational modifications near genes involved in cancer processes and in brain function. Here, we review possible mechanisms by which mutant H3.3 histones may act to promote tumorigenesis. Furthermore, we discuss how perturbations in normal H3.3 chromatin-related and epigenetic functions may more broadly contribute to the formation of human cancers.
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