Abstract
Simple SummaryRetinoblastoma 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.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.
Highlights
IntroductionIt can present in a unilateral form, where the disease develops in a single eye, or bilateral, where both eyes are affected
As invasive prenatal testing via chorionic villus sampling (CVS) or amniocentesis is only available from 11 and 16 weeks, respectively, noninvasive prenatal diagnosis (NIPD) has the advantage of an earlier diagnosis, as well as an absence of the reported 0.5% risk of miscarriage associated with invasive prenatal tests [36,37]
The application of both liquid biopsy and noninvasive prenatal diagnosis offers a wealth of new possibilities to retinoblastoma patients, and significant research has been published in this area in recent years (Table 1)
Summary
It can present in a unilateral form, where the disease develops in a single eye, or bilateral, where both eyes are affected. The age of onset is usually less than three years old, and for patients with bilateral disease, it is often significantly earlier, before 12 months of age [1]. While retinoblastoma is lethal if left untreated, it is considered highly curable in countries where early detection and multiple treatment modalities are available, resulting in disease-free survival rates over 97% [4]. In middleand lower-income countries this figure is significantly reduced, leading to an average global patient survival rate of less than 30% [5]
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