Epigenetic Factors in Pathogenesis of Retinoblastoma: DNA Methylation and Histone Acetylation

(Background) Retinoblastoma is the most common intraocular malignancy in childhood, primarily caused by mutations in the RB1 gene. However, increasing evidence highlights the significant role of epigenetic mechanisms, particularly DNA methylation and histone acetylation, in tumor initiation and progression. This review aims to summarize and critically assess recent findings on how DNA methylation and histone acetylation contribute to the pathogenesis of retinoblastoma, and to explore their potential role as diagnostic biomarkers and therapeutic targets. (Methods) We searched the databases PubMed, Scopus, and ScienceDirect following PRISMA guidelines. Eligible studies were English-language, open-access articles published within the last ten years, including cohort studies, research articles, and case reports. After rigorous screening, 18 studies were included in the final analysis. (Results) Aberrant DNA methylation was found to inactivate tumor suppressor genes (RB1, RASSF1A, p16INK4A, MGMT) and promote oncogenesis through hypermethylation of regulatory elements. Similarly, histone acetylation's dysregulation contributed to chromatin remodeling and overexpression of oncogenic factors such as SYK, GALNT8, and lincRNA-ROR. Elevated histone deacetylase (HDAC) activity was also linked to tumor cell proliferation, metastasis, and treatment resistance. Epigenetic inhibitors targeting these pathways demonstrated promising therapeutic potential. (Conclusions) DNA methylation and histone acetylation play a crucial role in the epigenetic regulation of genes implicated in retinoblastoma. Their dysregulation promotes tumorigenesis, and targeting these mechanisms represents a promising avenue for novel diagnostic and therapeutic strategies in pediatric oncology.