Mohammad Faizaan, Helin Kristian
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
The Novo Nordisk Center for Stem Cell Biology (Danstem), University of Copenhagen, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Genes Dev. 2017 Dec 1;31(23-24):2313-2324. doi: 10.1101/gad.309013.117.
One of the most striking results in the area of chromatin and cancer in recent years has been the identification of recurrent mutations in histone genes in pediatric cancers. These mutations occur at high frequency and lead to the expression of mutant histones that exhibit oncogenic features. Thus, they are termed oncohistones. Thus far, mutations have been found in the genes encoding histone H3 and its variants. The expression of the oncohistones affects the global chromatin landscape through mechanisms that have just begun to be unraveled. In this review, we provide an overview of histone mutations that have been identified and discuss the possible mechanisms by which they contribute to tumor development. We further discuss the targeted therapies that have been proposed to treat cancers expressing oncohistones.
近年来，染色质与癌症领域最引人注目的成果之一是在儿童癌症中发现了组蛋白基因的复发性突变。这些突变发生频率很高，导致突变组蛋白的表达，这些突变组蛋白具有致癌特征。因此，它们被称为致癌组蛋白。到目前为止，已在编码组蛋白H3及其变体的基因中发现了突变。致癌组蛋白的表达通过刚刚开始被揭示的机制影响整体染色质格局。在本综述中，我们概述了已鉴定出的组蛋白突变，并讨论了它们促进肿瘤发展的可能机制。我们还进一步讨论了已提出的用于治疗表达致癌组蛋白癌症的靶向疗法。
