Professor Jesse Berry determines the superiority of the aqueous humour as a source of tumour DNA and explains her findings from her CHECT-funded research.
Developing a liquid biopsy for retinoblastoma (Rb) would help us to overcome two current clinical problems: 1) our inability to directly biopsy tumour tissue from the eye; and 2) the resulting lack of measurable molecular diagnostic and prognostic information for Rb. In current practice, management and treatment decisions for Rb patients are based almost entirely on clinical findings and the judgment and experience of the treating clinician. A better understanding of 1) how to safely obtain and analyse genetic information from the tumour found in the aqueous humour (AH) and blood and 2) the clinically relevant specific molecular information within AH could revolutionise how we treat and care for retinoblastoma patients.
The goal of this project was to identify which biofluid (AH or blood) was most likely to contain DNA from the Rb tumour, and specifically changes, such as gain of chromosome 6p which is a marker of disease, which can have significance in deciding how to treat the tumour.
Findings from the look into aqueous humour as a source of tumour DNA
Our main finding at this time is that the AH has a higher amount and likelihood of finding circulating DNA compared to the blood. Of samples of aqueous humour taken at diagnosis, 89% of samples have detectable tumour DNA if the tumour is at least 3mm in size. Blood is much less likely to have this information. However it is not impossible, as 1/60 in this group showed 6p gain in the blood. This is actually a really significant finding – and as far as we know this is the first time that 6p gain has been identified in the blood. While the AH can provide important information about the risk to the child’s eye from this cancer, it is the blood that can provide crucial information about the risk to the child’s life. Thus, identifying 6p gain in the blood provides important evidence that there is a role for monitoring the blood for tumour DNA, as these children may be at increased risk of metastatic disease. Although this is rare in the US and UK, it is the most dreaded outcome in the care of children with Rb. Thus, with CHECT’s support, we have additional evidence that evaluating the blood is important and, in the future, may be used to guide any additional chemotherapy treatments the child may need.
The results of this study have the potential to not only impact clinical decision-making but to continue to move the field towards introducing personalised RB patient care – wherein decisions are made based not just on clinical findings, but on molecular information from the tumour (such as tumour DNA in the AH and/or the blood). With CHECT’s support, we have 12 new publications of our findings and multiple presentations at international conferences. We anticipate that the publication of these findings will encourage additional centres to adopt a liquid biopsy program for the management of patients with retinoblastoma. To read the full final report for this research go to https://chect.org.uk/research/previous-chect-research/.
Glossary:
Aqueous humour (AH): a clear fluid in the eye
Heritable: can be passed from parent to child
Biopsy: The removal of cells or tissues for examination by a pathologist (a scientist who studies the causes and effects of diseases,)
Liquid biopsy: a laboratory test done on a sample of body fluid to look for cancer cells
Cell-free DNA (cfDNA): fragments of DNA circulating in body fluids
Molecular biomarkers: certain molecules or set of molecules that can be of help for diagnosis or prognosis of diseases or disorders.
Diagnosis: identification of an illness by examination of the symptoms.
Prognosis: the likely course of a medical condition
Metastatic disease: cancer that spreads from where it starts to another part of the body