Further investigation into intra-ocular fluid as a liquid biopsy in retinoblastoma

Brief Lay background

Retinoblastoma is a rare type of eye cancer that starts in the retina, the light-sensitive tissue at the back of the eye. It mainly affects young children under the age of five.

One in 20,000 children in the UK is affected by retinoblastoma. While most of these children will be successfully treated, some may lose their vision in the affected eye(s) or need to have the eye removed.

What problem/knowledge gap does it help address

Retinoblastoma can occur as an inherited or a non-inherited condition. In the majority of inherited cases, the child will have received a faulty copy of the RB1 gene from one of their parents.

Children with non-hereditary retinoblastoma are born with two healthy copies of the RB1 gene. However, both copies of the gene then acquire faults that lead to the development of cancer. These gene faults only affect the eye and can’t be passed to future generations.

Determining whether a child with retinoblastoma has inherited or acquired faults in the RB1 gene is important for determining any further cancer risk – both for the child and their siblings. But this diagnosis requires a sample of DNA from tumour – which is only available if a child needs to have their eye removed as part of their treatment.

Aim of the project

To advance the development of a new diagnostic and monitoring test for retinoblastoma using DNA extracted from eye fluid.

Key procedures/objectives

1. Collect eye fluid from retinoblastoma patients undergoing treatment – as well as from children undergoing routine surgery for an unrelated eye condition.
2. Analyse the levels of cell-free DNA (cfDNA) in samples – and perform an established next-generation sequencing assay to look for any acquired faults in the RB1 gene and surrounding regions.
3. Identify the optimal timing for collecting the sample – and determine whether monitoring of cfDNA levels and/or genetic profiles could help inform treatment decisions.

Potential impact on people with sight loss

Developing a new test that can accurately diagnose the root cause of a child’s retinoblastoma even when the tumour DNA is unavailable would have a significant impact on their treatment and follow-up care. It would also help to inform genetic counselling for their families – helping them to better plan for the future.