Analysing DNA to provide accurate diagnoses and help predict the outcome of retinoblastoma (Rb)

Brief Lay Background

Retinoblastoma is a childhood eye cancer, which usually occurs before the age of three. It is almost always caused by defects in a gene called RB1. These defects can be identified through genetic sequencing of DNA taken from the blood and/or tumour of retinoblastoma patients. Currently, the only way to analyse tumour DNA is by removing the eye, so affected children have to go under general anaesthetic.

Because treatments are improving, eye removal is now less necessary. Therefore, tumour DNA is not available for many patients and the genetic basis of retinoblastoma cannot be confirmed. This can affect whether clinicians can predict the likelihood that a patient will get a tumour in their second eye or in other parts of their body later in life. In some cases, retinoblastoma can be inherited and therefore a genetic diagnosis is needed to be able to determine if family members are at risk from the disease.

What problem/knowledge gap does it help address

The researchers will investigate more eye fluid samples from retinoblastoma patients to make the test as reliable and cost efficient as possible so it can be introduced into clinical service. The team have already set up a collaboration with the Barts Health NHS Trust, which are the second retinoblastoma service in the UK, in order to be able to include as many patients as possible in the research.

Aim of the research project

To investigate the use of small quantities of DNA from ocular fluid to reliably diagnose retinoblastoma.

Key procedures/objectives

1. Determine the most cost effective and reliable platform for detection of Rb in small quantities of DNA from eye fluid.
2. Assess small quantities of DNA to predict outcomes
3. Assess small quantities of DNA to identify whether there is advanced or metastatic disease
4. Implement this method as standard clinical practice if deemed suitable

Potential impact on people with sight loss

This test will mean that researchers will be able to identify Rb in patients who have not had their eye removed. As a result, fewer children will need to undergo a general anaesthetic – a necessary requirement for full eye examinations. They can also be told that they are not at risk of other cancers later in life and other family members are not themselves at risk of retinoblastoma.

If tests can be developed that can predict how well a patient will respond to treatment and detect whether the cancer has spread, it would help clinicians decide what is the best course of treatment for a patient, including whether to remove an eye immediately or give chemotherapy to the whole body.