Open AccessEpigenetic modifiers: activities in renal cell carcinoma
Author(s) -
Aguirre A. de Cubas,
W. Kimryn Rathmell
Publication year - 2018
Publication title -
nature reviews. urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.972
H-Index - 81
eISSN - 1759-4820
pISSN - 1759-4812
DOI - 10.1038/s41585-018-0052-7
Subject(s) - chromatin , epigenetics , carcinogenesis , histone , computational biology , biology , chromatin remodeling , arid1a , genetics , bap1 , epigenomics , bivalent chromatin , cancer research , gene , medicine , mutation , dna methylation , gene expression
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.