Data from BCOR Mutations Deregulate Cell Cycle and Hypoxic Adaptation Pathways in Retinoblastoma
Year: 2026
Type: other
Abstract: Retinoblastoma is the most common pediatric eye cancer. Most cases of retinoblastoma are initiated by biallelic mutational inactivation of the RB1 gene, yet most retinoblastoma tumors harbor additional genomic aberrations that may promote tumor progression. After RB1, the gene that is most commonly mutated gene in retinoblastoma is BCOR, which is mutated in approximately 20% of retinoblastoma tumors and is associated with a more aggressive tumor phenotype and worse patient outcomes. Despite its importance, little is known about the role of BCOR in retinoblastoma. In this study, we interrogated BCOR in low-passage retinoblastoma cell lines using mass spectrometry, chromatin immunoprecipitation sequencing, and RNA sequencing. We show that the BCOR protein interacts with members of the noncanonical polycomb repressive complex 1.1 and localizes at gene loci with traditionally activating and repressing chromatin markers. Loss of BCOR downregulates the expression of genes associated with cell-cycle regulation and upregulates genes associated with hypoxic adaptation. We conclude that BCOR mutations slow cell proliferation and drive hypoxic adaptation in retinoblastoma via epigenetic mechanisms that may be amenable to targeted therapy. Implications: This study reveals that BCOR may play a noncanonical, multifaceted role in retinoblastoma with implications in cell cycle, differentiation, and hypoxic adaptation, ultimately shedding insight into its molecular framework for future therapeutic strategies.
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W7133343495