Chromatin Regulators In Retinoblastoma: Biological Roles And Therapeutic Applications

Retinoblastoma (RB) is a pediatric ocular tumor mostly occurring due to the biallelic loss ofRB1gene in the developing retina. Early studies of genomic aberrations in RB have provided a valuable insight into how RB can progress following the tumor-initiatingRB1mutations and have established a notion that inactivation ofRB1gene is critical to initiate RB but this causative genetic lesion alone is not sufficient for malignant progression. With the advent of high-throughput sequencing technologies, we now have access to the comprehensive genomic and epigenetic landscape of RB and have come to appreciate that RB tumorigenesis requires both genetic and epigenetic alterations that might be directly or indirectly driven byRB1loss. This integrative perspective on RB tumorigenesis has inspired research efforts to better understand the types and functions of epigenetic mechanisms contributing to RB development, leading to the identification of multiple epigenetic regulators misregulated in RB in recent years. A complete understanding of the intricate network of genetic and epigenetic factors in modulation of gene expression during RB tumorigenesis remains a major challenge but would be crucial to translate these findings into therapeutic interventions. In this review, we will provide an overview of chromatin regulators identified to be misregulated in human RB among the numerous epigenetic factors implicated in RB development. For a subset of these chromatin regulators, recent findings on their functions in RB development and potential therapeutic applications are discussed.