New type of Rb

CHECT photo - retinoblastoma past research

A new type of retinoblastoma

In 2013 a ‘new type of Rb’ was revealed by Dr. Brenda Gallie at the Princess Margaret Cancer Centre, University Health Network, in Canada. Rb specialists in the UK provided the following information about the impact of this on UK patients.

The data regarding this was first presented at a conference in Buenos Aires in 2011. The full paper, published early 2013, gives a better idea of the numbers involved, which are very small and it looks likely that this may be relevant in 1-2% of non heritable forms of retinoblastoma.

As we know it up to now, the retinoblastoma gene, more accurately described as the ‘retinoblastoma predisposition gene’ or ‘RB1’, is one of a pair of such genes. Everyone has a pair of all of the chromosomes except X and Y, and one copy of this gene is present on the long arm of each pair of chromosomes, 13 in most of the general population.

The role of RB1 has been thought to prevent the development of certain tumours, particularly retinoblastoma and the other tumours such as bone and soft tissue sarcomas which people who have the heritable form of retinoblastoma are at a slightly higher risk of developing. As such, RB1 is an ‘anti-oncogene’ (because it is preventative) as distinct from an ‘oncogene’ (which is causative).

We only need one copy of RB1 to prevent the tumour but loss or damage to both allows retinoblastoma or sarcoma etc to develop in any affected cell. As yet, we do not know exactly how the gene prevents retinoblastoma or, put another way, how its absence allows it to develop.

This new gene appears to be a causative oncogene. It seems to be able to induce retinoblastoma in the presence of normal anti-oncogene. Extra-expression of a gene which tends to cause cancer (in this case the N-myc), possibly with other genetic changes, may cumulatively override the tumour-suppressing effect of the Rb gene.

It seems also to induce unilateral tumours at a much earlier age than normal. It is still unclear if the N-myc gene amplification is the underlying cause though or just a marker of a different ‘non-Rb gene’ cause. This discovery may help to distinguish patients with a rare variant of unilateral retinoblastoma which is unlikely to be associated with a risk of Rb in the other eye or elsewhere in the body.

Testing for it may reduce the need for onerous surveillance – once it is sure that the presenting tumour has been adequately treated – and screening of siblings and offspring.

The new gene only affects a small proportion of very young children who present unusually early with non-familial unilateral retinoblastoma. It is not thought likely to affect treatment at this stage.


This type of testing has been undertaken in UK for some time when investigating certain other none Rb tumours. These tests are carried on tumour tissue and not blood and therefore would only be possible post enucleation.

Birmingham Children’s Hospital and Royal London Hospital consultant geneticists Dr Trevor Cole and Dr Elisabeth Rosser confirmed that this testing on retinoblastoma tumour tissue would be carried out on those small number of enucleated cases where no Rb gene mutations are identified.

Many thanks to the following people for helping compile this report: Mr Mandeep Sagoo, Dr Elisabeth Rosser, Dr Trevor Cole, Mr John Hungerford and Mr John Ainsworth.