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H3G34 mutations occur in both pediatric non-brainstem high-grade gliomas (G34R/V) and giant cell tumors of bone (G34W/L). Glioblastoma patients with G34R/V mutation have a generally adverse prognosis, whereas giant cell tumors of bone are rarely metastatic benign tumors. G34 mutations possibly disrupt the epigenome by altering H3K36 modifications, which may involve attenuating the function of SETD2 at methyltransferase. H3K36 methylation change may further lead to genomic instability, dysregulated gene expression pattern, and more mutations. In this chapter, we summarize the pathological features of each mutation type in its respective cancer, as well as the potential mechanism of their disruption on the epigenome and genomic instability. Understanding each mutation type would provide a thorough background for a thorough understanding of the cancers and would bring new insights for future investigations and the development of new precise therapies.


Lei Qiu, Junhong Han. Histone H3G34 Mutation in Brain and Bone Tumors. Advances in experimental medicine and biology. 2021;1283:63-71

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PMID: 33155138

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