The last decade’s progress unraveling the mutational landscape of all age groups of cancer has uncovered mutations in histones as vital contributors of tumorigenesis. Here we review three new aspects of oncogenic histones: first, the identification of additional histone mutations potentially contributing to cancer formation; second, tumors expressing histone mutations to study the crosstalk of post-translational modifications, and; third, development of sophisticated biological model systems to reproduce tumorigenesis. At the outset, we recapitulate the firstly discovered histone mutations in pediatric and adolescent tumors of the brain and bone, which still remain the most pronounced histone alterations in cancer. We branch out to discuss the ramifications of histone mutations, including novel ones, that stem from altered protein-protein interactions of cognate histone modifiers as well as the stability of the nucleosome. We close by discussing animal models of oncogenic histones that reproduce tumor formation molecularly and morphologically and the prospect of utilizing them for drug testing, leading to efficient treatment and cure of deadly cancers with histone mutations.

中文翻译：

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致癌组蛋白的机制 GEMM。

过去十年在揭示所有年龄组癌症突变情况方面取得的进展揭示了组蛋白突变是肿瘤发生的重要因素。在这里，我们回顾了致癌组蛋白的三个新方面：首先，鉴定可能导致癌症形成的其他组蛋白突变；第二，表达组蛋白突变的肿瘤以研究翻译后修饰的串扰，以及；第三，开发复杂的生物模型系统来重现肿瘤发生。首先，我们回顾了在儿童和青少年脑和骨肿瘤中首次发现的组蛋白突变，这些突变仍然是癌症中最明显的组蛋白改变。我们扩展讨论组蛋白突变的后果，包括新的突变，这源于同源组蛋白修饰剂的蛋白质-蛋白质相互作用的改变以及核小体的稳定性。我们最后讨论了致癌组蛋白的动物模型，这些模型在分子和形态上复制肿瘤形成，以及利用它们进行药物测试的前景，从而有效治疗和治愈具有组蛋白突变的致命癌症。