Abstract：
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.
摘要：
视网膜母细胞瘤(RB),起源于发育中的视网膜，是儿童期侵袭性眼内恶性肿瘤。RB1的双等位基因损失通常被认为是在大多数RB情况下启动RB发育的先决条件。建议需要由RB1突变后的基因组不稳定性引起的其他基因突变来促进RB发育。高通量测序技术的最新进展使人们对RB的病因有了更深入和更全面的了解，RB1双等位基因丢失后的其他遗传改变很少见，然而,由RB1丢失驱动的表观遗传变化成为促进RB肿瘤发生的重要因素.已发现多种表观遗传调节因子失调并有助于RB发育。包括非编码RNA，DNA甲基化,RNA修饰，染色质构象,和组蛋白修饰。充分了解RB形成中遗传和表观遗传改变的作用对于促进将这些发现转化为RB的有效治疗策略至关重要。在这次审查中,我们总结了当前有关RB遗传缺陷和表观遗传失调的知识，旨在帮助了解它们在RB肿瘤发生中的联系和作用。
