Department of Human Genetics, McGill University, Montreal, QC, H3A 0C7, Canada.
Department of Human Genetics, McGill University, Montreal, QC, H3A 0C7, Canada; Department of Pediatrics, McGill University, Montreal, QC, H3A 0C7, Canada; The Research Institute of the McGill University Health Centre, Montreal, QC, H4A 3J1, Canada.
Trends Cancer. 2023 May;9(5):444-455. doi: 10.1016/j.trecan.2023.02.003. Epub 2023 Mar 16.
Recurrent somatic mutations in histone 3 (H3) variants (termed 'oncohistones') have been identified in high-grade gliomas (HGGs) in children and young adults and induce tumorigenesis through disruption of chromatin states. Oncohistones occur with exquisite neuroanatomical specificity and are associated with specific age distribution and epigenome landscapes. Here, we review the known intrinsic ('seed') and the extrinsic ('soil') factors needed for their optimal oncogenic effect and highlight the many unresolved questions regarding their effects on development and crosstalk with the tumor microenvironment. The 'seed and soil' analogy, used to explain tumor metastatic niches, also applies to oncohistones, which mainly thrive and flourish in specific chromatin states during very narrow windows of development, creating exquisite vulnerabilities, which could provide effective therapies for these deadly cancers.
组蛋白 3（H3）变体（称为“癌组蛋白”）的复发性体细胞突变已在儿童和年轻成人的高级别神经胶质瘤（HGG）中被鉴定出来，并通过破坏染色质状态诱导肿瘤发生。癌组蛋白具有精细的神经解剖学特异性，与特定的年龄分布和表观基因组景观相关。在这里，我们回顾了已知的内在（“种子”）和外在（“土壤”）因素，这些因素对于它们的最佳致癌效应是必需的，并强调了许多关于它们对发育的影响和与肿瘤微环境相互作用的未解决问题。用于解释肿瘤转移龛的“种子和土壤”类比也适用于癌组蛋白，癌组蛋白主要在发育的非常狭窄的窗口期间在特定的染色质状态中茁壮成长，从而产生精细的脆弱性，这可能为这些致命癌症提供有效的治疗方法。
