Resumen
Aqueous humor (AH) liquid biopsy is an enriched source of cell-free circulating tumor-derived DNA for retinoblastoma (RB). The use of this AH liquid biopsy allows for genomic analysis of eyes in the absence of tumor tissue. Development of this platform was critical because direct tumor biopsy is prohibited in RB due to risk of extraocular tumor spread. In this retrospective study, we provide comprehensive, whole-genome analysis of the somatic copy number alterations (SCNAs) in 68 eyes of 64 RB patients. We show that the prevalence of specific SCNAs differ between eyes that required immediate enucleation (surgical removal) and eyes that were attempted to be saved but subsequently failed treatment, requiring secondary enucleation. Increases in chromosomal instability, or higher number of broad genomic alterations, predict higher risk clinical and biomarker features in these eyes. Prospective analyses are needed to further determine the clinical relevance and application of these findings.