LAUSR

Simple Summary Retinoblastoma is a childhood eye cancer caused almost entirely by defects in a gene known as RB1. Other genetic changes within the tumour are also thought to affect the progression of disease. Until recently, tumour DNA could only be analysed if the eye was removed as part of patient treatment. However, recent research has shown that the analysis of a particular type of DNA, known as cell-free DNA, within the eye fluid or blood of patients, can be used to detect changes in the RB1 gene or other parts of the genome within a retinoblastoma tumour. The analysis of cell-free DNA in the blood of pregnant women can also be used to detect whether the unborn baby will be affected with retinoblastoma. In this review, we summarise these studies and discuss the potential impact of cell-free DNA analysis on retinoblastoma patient management in the future. Abstract Retinoblastoma is a childhood eye cancer, mainly caused by mutations in the RB1 gene, which can be somatic or constitutional. Unlike many other cancers, tumour biopsies are not performed due to the risk of tumour dissemination. As a result, until recently, somatic genetic analysis was only possible if an affected eye was removed as part of a treatment. Several recent proof of principle studies have demonstrated that the analysis of tumour-derived cell-free DNA, either obtained from ocular fluid or blood plasma, has the potential to advance the diagnosis and influence the prognosis of retinoblastoma patients. It has been shown that a confirmed diagnosis is possible in retinoblastoma patients undergoing conservative treatment. In vivo genetic analysis of retinoblastoma tumours is also now possible, allowing the potential identification of secondary genetic events as prognostic biomarkers. In addition, noninvasive prenatal diagnosis in children at risk of inheriting retinoblastoma has been developed. Here, we review the current literature and discuss the potential impact of cell-free DNA analysis on both the diagnosis and treatment of retinoblastoma patients and their families.