视网膜母细胞瘤（RB）起源于正在发育的视网膜，是一种侵袭性的儿童期眼内恶性肿瘤。在大多数 RB 病例中，RB1 的双等位基因丢失通常被认为是启动 RB 发育的先决条件。 RB1 突变后基因组不稳定引起的额外基因突变被认为是促进 RB 发育所必需的。高通量测序技术的最新进展使人们能够更深入、更全面地了解 RB 的病因学，即 RB1 双等位基因丢失后的额外遗传改变很少见，但 RB1 丢失驱动的表观遗传变化成为促进 RB 肿瘤发生的关键因素。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。充分了解遗传和表观遗传改变在 RB 形成中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。在这篇综述中，我们总结了有关 RB 遗传缺陷和表观遗传失调的当前知识，旨在帮助了解它们在 RB 肿瘤发生中的联系和作用。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

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.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.