Molecular assessment of Rb gene mosaicism V.2
Research type
Research Study
Full title
Molecular assessment of Rb gene mosaicism in the optic nerve
IRAS ID
92610
Contact name
John Ross AINSWORTH
Contact email
Sponsor organisation
Birmingham Children's Hospital
Research summary
Retinoblastoma is a cancer of children’s eyes that is fatal without treatment. It is caused by the loss of Rb1 tumour suppressor gene function. Homozygous Rb1 gene loss prevents production of Rb protein, an inhibitor of cell division.
Mutation detection in blood and tumour is intrinsic to clinical care for all UK retinoblastoma patients. Secondary benefit to the wider family from gene studies increases as testing becomes increasingly informative. Exclusion of an a priori risk means far fewer relatives need to undergo screening by regular eye examination, many of whom would have required multiple general anaesthetics throughout early childhood before gene testing was available.
However, the child in whom the retinoblastoma developed requires continuing monitoring after we have cured the original cancer, due to the risk of retinoblastoma developing in the other eye, and risk of primary cancers elsewhere in the body. If we are able to demonstrate that the child has no increased risk of such tumours then we hypothesise that such monitoring, often involving multiple general anaesthetics, may not be necessary. Currently, we can find out whether children have a faulty retinoblastoma gene throughout their body (germline mutation), but currently we cannot reliably detect the presence or extent of a mosaic mutation. As a consequence exclusion of mutations identified within the intraocular Rb (IOR), from a blood sample, does not provide absolute evidence of exclusion from the contra-lateral eye, or indeed other tissues.
We wish to investigate whether we are able to test part of a pathology specimen, outside the eye (ie optic nerve), but obtained during routine care, carries the identified IOR Rb gene mutations.
The study repeats routinely undertaken tests on a different tissue (optic nerve), as well as IOR. No novel tests are performed, only the same test on a different region of the same surgical specimen.REC name
West Midlands - Solihull Research Ethics Committee
REC reference
13/WM/0253
Date of REC Opinion
20 Aug 2013
REC opinion
Further Information Favourable Opinion