Assessment of cell-free DNA in the management of retinoblastoma
Research type
Research Study
Full title
Assessment of cell-free DNA from blood or non-haematological fluids that could be utilised for genetic testing and prognostication in Retinoblastoma
IRAS ID
189947
Contact name
Manoj Parulekar
Contact email
Sponsor organisation
Birmingham Children's Hospital NHS Foundation Trust
Duration of Study in the UK
1 years, 6 months, 0 days
Research summary
Retinoblastoma is the most common eye malignancy of childhood, affecting 1 in 20,000 children, typically presenting before the age of 5. Retinoblastoma can be either inherited (a germline mutation) or sporadic (somatic mutation).
Bilateral retinoblastoma is due to germline mutations present in all body cells, therefore increasing the risk of secondary non-ocular malignancies. Unilateral tumours are most commonly the result of somatic mutations (these occur post fertilisation and only affect a percentage of cells), however in 15% of unilateral cases there is a germline mutation. Differentiating which unilateral tumours are resultant of somatic or germline mutations would improve prediction of future recurrence of retinoblastoma in the unaffected eye and risk of second non-ocular primary malignancies.
Furthermore proof that a retinoblastoma is due to a somatic mutation (i.e not inherited), has a significant positive impact on the family, confirming that siblings of affected children would not require frequent hospital appointments for examination under general anaesthesia. Best practice dictates these would be required if the inherited form of retinoblastoma had not been excluded. Such exclusion is becoming less frequent as improved non surgical treatment means fewer eyes are enucleated which prevents genetic testing of the cancer.
In some patients recurrent aqueous taps are required for future chemotherapy or cerebro-spinal fluid collected to exclude CNS dissemination. All or a proportion of such fluid is routinely discarded.
Analysis of cell free DNA (cfDNA) from retinoblastoma patients undergoing intra-ocular chemotherapy (IOC), diagnostic CSF taps, and from routine paediatric cataracts operations would be compared to peripheral blood DNA sampled taken peri-operatively, looking for mutations in the Retinoblastoma gene.
An initial pilot study is required to confirm the concentration of DNA in the fluids tested comparing eyes with and without retinoblastoma to confirm the technologies analytical validity without significant errors from false positive or negative results .
REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
16/EE/0528
Date of REC Opinion
3 Jan 2017
REC opinion
Further Information Favourable Opinion