Developing the use of cell-free DNA analysis for the diagnosis of retinoblastoma

Project leads Amy Gerrish, Stephanie Allen.

Watch Dr Amy Gerrish - Transforming the treatment of children's eye cancer

We are a leading centre in the development of genetic diagnosis of retinoblastoma, the most common childhood eye cancer, using cell-free DNA analysis. We were the first worldwide to show that genetic variation in the causal gene (RB1), can be identified within a retinoblastoma tumour, through the analysis of cell-free DNA taken from eye fluid. These changes can currently only be detected if an affected eye is removed as part of treatment. In the last 10 years, the incidence of eye removal has significantly reduced due to improved treatment options.

Identification of RB1 changes in the tumour allows clinicians to determine the risk of a child developing cancer in the second eye and additional cancers later in life. As retinoblastoma can be inherited, identification of the type of RB1 variation with a retinoblastoma tumour also determines whether siblings of a patient could be at risk of acquiring the disease themselves. We are currently developing this test for implementation into clinical service. We are also investigating whether the identification of other genetic changes in the retinoblastoma tumour can predict how well it will respond to certain treatments.

We are also investigating whether the identification of other genetic changes in the retinoblastoma tumour can predict how the disease might develop or how well it will respond to certain treatments. Since 2023, we have also expanded our work to analyse cell-free DNA from the blood of retinoblastoma patients, as well as eye fluid. These projects have involved collaboration with several partners including the University of Birmingham, other NHS Trusts (Barts, GOSH) as well as international retinoblastoma centres across Germany, France, Switzerland, The Netherlands and Spain.

We have also developed non-invasive prenatal diagnosis (NIPD) for babies at risk of heritable retinoblastoma. This involves the detection of fetal-derived cell-free DNA in the blood of pregnant women. Such a test can avoid urgent post-natal testing and reduce family stress. Since 2016 we have offered this test for babies whose father or sibling has been affected with retinoblastoma. We have recently developed NIPD testing for babies of previously affected mothers and we have been offering this as a clinical service since April 2022.

Grants

2023

Fight for Sight
The use of cell-free DNA analysis to provide an accurate genetic diagnosis and aid the prediction of prognosis in retinoblastoma (£245,479)

Fight Kids Cancer
Collaborative study to identify Biomarkers to adjust treatment intensity for children with Retinoblastoma (CoBioRB) (€61,000)

NIHR GOSH BRC
Further development of BWC cell-free DNA assays using Oxford Nanopore Technologies (ONT) (£114,000)

2021-2022

Fight for Sight/CHECT
Further investigation into intra-ocular fluid as a liquid biopsy in retinoblastoma (£14,851)

2019-2021

Birmingham Children’s Hospital Research Foundation
Clinical implementation of non-invasive testing in retinoblastoma (£55,399)

2016-2019

Welcome Pathfinder award
Retinoblastoma: screening for RB1 mutations by intraocular cell free DNA analysis (£146,210)

Key Publications

Gerrish A, Mashayamombe-Wolfgarten C, Stone E, Román-Montañana C, Abbott J, Jenkinson H, Millen G, Gurney S, McCalla M, Staveley SJ, Kainth A, Kirk M, Bowen C, Cavanagh S, Bunstone S, Carney M, Mohite A, Clokie S, Reddy MA, Foster A, Allen S, Parulekar M, Cole T. Genetic Diagnosis of Retinoblastoma Using Aqueous Humour-Findings from an Extended Cohort. Cancers (Basel). 2024 Apr 19;16(8):1565. doi: 10.3390/cancers16081565. PMID: 38672657; PMCID: PMC11049382.

Gerrish A, Jenkinson H, Cole T. The Impact of Cell-Free DNA Analysis on the Management of Retinoblastoma. Cancers (Basel). 2021 Mar 29; 13(7):1570. doi: 10.3390/cancers13071570. PMID: 33805427; PMCID: PMC8037190.

Gerrish A, Bowns B, Mashayamombe-Wolfgarten C, Young E, Court S, Bott J, McCalla M, Ramsden S, Parks M, Goudie D, Carless S, Clokie S, Cole T, Allen S. Non-Invasive Prenatal Diagnosis of Retinoblastoma Inheritance by Combined Targeted Sequencing Strategies. J Clin Med. 2020 Oct 30; 9(11):3517. doi: 10.3390/jcm9113517. PMID: 33143217; PMCID: PMC7692133.

*Gerrish A, Stone E, Clokie S, Ainsworth JR, Jenkinson H, McCalla M, Hitchcott C, Colmenero I, Allen S, Parulekar M, Cole T. Non-invasive diagnosis of retinoblastoma using cell-free DNA from aqueous humour. Br J Ophthalmol. 2019 May; 103(5): 721–724. doi: 10.1136/bjophthalmol-2018-313005. PMID: 30745306, PMCID: PMC6709774.

*Received the 2020 Ulverscroft David Owen prize for best published paper in paediatric ophthalmology research (https://www.rcophth.ac.uk/news-views/rcophth-and-ulverscroft-foundation-announce-winner-of-the-ulverscroft-david-owen-prize/)