Abstract 1672: Effect of BCOR loss in Xenopus laevis and tropicalis: Insights for retinal development and retinoblastoma

Abstract Retinoblastoma is the most common pediatric eye cancer, accounting for approximately 11% of cancers within the first year of life. Almost all retinoblastoma tumors are initiated by bi-allelic mutational inactivation of RB1, yet there is a broad range of clinical presentations, suggesting the existence of secondary driver events in cancer progression. Genomic analysis identified BCOR as the second most commonly mutated gene in retinoblastoma. There is growing evidence that inactivating BCOR mutations are associated with more aggressive features, such as dedifferentiation, vitreous seeding, optic nerve invasion, and worse patient outcomes. Unfortunately, little is known about the function of BCOR in the retina and the effects of BCOR loss in retinoblastoma. Here, we used Xenopus laevis and tropicalis models to study the role of BCOR in normal ocular and retinal development. In both models, targeted depletion of BCOR in cell lineages giving rise to the eye resulted in a discrete microphthalmia phenotype. Furthermore, we developed in situ hybridization tools for probing characteristic retinal lineage-specific genes and performed histology to compare structural differences. We provide evidence that BCOR normally regulates critical steps in retinal developmental, suggesting that loss of BCOR in retinoblastoma may drive tumor progression by disrupting this function. Citation Format: Michelle Garying Zhang, Dawn Owens, Nicole Jones, Daniel Pelaez, J. William Harbour. Effect of BCOR loss in Xenopus laevis and tropicalis: Insights for retinal development and retinoblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1672.