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

Project leads: Amy Gerrish, Stephanie Allen, Trevor Cole.

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, though 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.

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

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 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 this will be available as a clinical service from 2022.



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 for Sight/CHECT

Further investigation into intra-ocular fluid as a liquid biopsy in retinoblastoma. (£14,851)



Birmingham Children’s Hospital Research Foundation

Clinical implementation of non-invasive testing in retinoblastoma. (£55,399)



Wellcome Pathfinder award

Retinoblastoma: screening for RB1mutations by intraocular cell free DNA analysis. (£146,210)


Key Publications

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 (


Further links

May 2022

January 2022

September 2021

August 2021


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