Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet

Wellcome Trust Sanger Institute, Hinxton, UK.
Nature Genetics (Impact Factor: 29.35). 04/2009; 41(5):521-3. DOI: 10.1038/ng.349
Source: PubMed


Somatically acquired epigenetic changes are present in many cancers. Epigenetic regulation is maintained via post-translational modifications of core histones. Here, we describe inactivating somatic mutations in the histone lysine demethylase gene UTX, pointing to histone H3 lysine methylation deregulation in multiple tumor types. UTX reintroduction into cancer cells with inactivating UTX mutations resulted in slowing of proliferation and marked transcriptional changes. These data identify UTX as a new human cancer gene.

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Available from: Giovanni Tonon
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    • "Although such mutations have not been reported so far in MM, EZH2 is clearly overexpressed in MM cells and contributes to cell survival [9]. This is consistent with data reporting the enrichment for H3K27me3 marked genes [10] as well as the finding of prevalent mutations of the H3K27-demethylase UTX [11] in MM cells. Although the functional role of EZH2 in maintaining the survival of MM cells is unknown, it has been shown that depletion of EZH2 could trigger apoptosis. "
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    • "Hence, understanding DNA methylation patterns is critical. Similarly, H3K27me3 is important to investigate because it has repeatedly been shown to be an powerful repressive epigenetic mark in promoters, the underlying enzymes controlling this mark are known to be dysregulated or mutated in many cancers [11], and changes in the distribution of this mark are important in differentiation of neural stem cells [12]. In some BTSCs, EZH2, a key member of the PRC2 complex that mediates the production of H3K27me3 marks, is upregulated and plays a pivotal role in glioblastoma tumor growth [13]. "
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