Epigenetic modifiers: activities in renal cell carcinoma.
Epigenetic modifiers: activities in renal cell carcinoma.
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DOI：
10.1038/s41585-018-0052-7
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Rathmell WK
中科院分区：
文献类型：
--
作者：
de Cubas AA;Rathmell WK
肾细胞癌（RCC）是一组多样化的恶性肿瘤，最近通过高通量测序工作显示，这些恶性肿瘤在许多染色质修饰基因（包括PBRM 1、SETD2、BAP 1、KDM 5C、KDM 6A和MLL2）中存在突变。目前的研究重点是了解染色质修饰剂用于抑制肿瘤发生的生物学活性，并开发利用这些知识的临床方法。不出所料，几个共同的主题统一了这些表观遗传修饰剂的功能，特别是组蛋白翻译后修饰和核小体组织的调节。此外，染色质修饰剂还控制着DNA修复和维持基因组完整性的关键过程，以及剪接和其他关键过程的调节。许多染色质修饰剂在细胞骨架调节中具有额外的非经典作用，这进一步促进了基因组稳定性，扩大了可能在肿瘤发生中必不可少的功能库。我们对染色质修饰物突变如何促进RCC肿瘤发生的理解正在提高，但仍然是一个深入研究的领域。重要的是，阐明染色质修饰剂的活性为RCC中新的治疗干预措施的开发提供了有趣的机会。
Renal cell carcinomas (RCCs) are a diverse set of malignancies that have recently been shown to harbour mutations in a number of chromatin modifier genes — including PBRM1, SETD2, BAP1, KDM5C, KDM6A, and MLL2 — through high-throughput sequencing efforts. Current research focuses on understanding the biological activities that chromatin modifiers employ to suppress tumorigenesis and developing clinical approaches that take advantage of this knowledge. Unsurprisingly, several common themes unify the functions of these epigenetic modifiers, particularly regulation of histone post-translational modifications and nucleosome organization. Furthermore, chromatin modifiers also govern processes crucial for DNA repair and maintenance of genomic integrity, as well as the regulation of splicing and other key processes. Many chromatin modifiers have additional noncanonical roles in cytoskeletal regulation, which further contribute to genomic stability, expanding the repertoire of functions that might be essential in tumorigenesis. Our understanding of how mutations in chromatin modifiers contribute to tumorigenesis in RCC is improving, but remains an area of intense investigation. Importantly, elucidating the activities of chromatin modifiers offers intriguing opportunities for the development of new therapeutic interventions in RCC.
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