Etiology including epigenetic defects of retinoblastoma

作者：Linbin Zhou, Yan Tong, Bo Man Ho, Jiahui Li, H Chan, Tian Zhang, Lin Du, Jing He, Li Jia Chen, Clement C. Tham, Jason C. Yam, Chi Pui Pang, Wai Kit Chu · 发表于：Asia-Pacific Journal of Ophthalmology · 年份：2024 · DOI：10.1016/j.apjo.2024.100072 · 被引用次数：8 · 研究领域：Epigenetics and DNA Methylation、Ocular Oncology and Treatments、Cancer-related Molecular Pathways

Retinoblastoma (RB), originating from the developing retina, is an aggressive intraocular malignant neoplasm in childhood. Biallelic loss of RB1 is conventionally considered a prerequisite for initiating RB development in most RB cases. Additional genetic mutations arising from genome instability following RB1 mutations are proposed to be required to promote RB development. Recent advancements in high throughput sequencing technologies allow a deeper and more comprehensive understanding of the etiology of RB that additional genetic alterations following RB1 biallelic loss are rare, yet epigenetic changes driven by RB1 loss emerge as a critical contributor promoting RB tumorigenesis. Multiple epigenetic regulators have been found to be dysregulated and to contribute to RB development, including noncoding RNAs, DNA methylations, RNA modifications, chromatin conformations, and histone modifications. A full understanding of the roles of genetic and epigenetic alterations in RB formation is crucial in facilitating the translation of these findings into effective treatment strategies for RB. In this review, we summarize current knowledge concerning genetic defects and epigenetic dysregulations in RB, aiming to help understand their links and roles in RB tumorigenesis.