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 on 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 non-canonical 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.

肾细胞癌 (RCC) 是一组多样化的恶性肿瘤，最近已证明它们在许多染色质修饰基因中存在突变——包括PBRM1、SETD2、BAP1、KDM5C、KDM6A和MLL2——通过高通量测序工作。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活性，以及​​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符的功能，特别是对组蛋白翻译后修饰和核小体组织的调控。此外，染色质修饰剂还控制着 DNA 修复和维持基因组完整性以及调节剪接和其他关键过程的关键过程。许多染色质修饰剂在细胞骨架调节中具有额外的非规范作用，这进一步有助于基因组的稳定性，扩展可能对肿瘤发生至关重要的功能库。我们对染色质修饰剂突变如何促进 RCC 肿瘤发生的理解正在改善，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 新治疗干预措施的开发提供了有趣的机会。