Genetic testing
Genetic testing and counselling for retinoblastoma
Genetic testing can:
- Inform a newly diagnosed person, and their family, of their genetic status (ie whether they have the heritable or non-heritable form of retinoblastoma).
- Clarify the chances of other children (eg siblings) having retinoblastoma. A brother or sister or a child of someone with retinoblastoma should have regular eye examinations until they are five unless genetic testing can show that the child has not inherited the altered gene.
- Clarify the situation for unaffected people in families where other members are affected by retinoblastoma.
- Test a pregnancy to know whether the foetus has a chance of developing retinoblastoma. This can only be offered if prior testing has identified the gene alteration.
What laboratory tests can be done?
The tests done in retinoblastoma can be divided into three groups:
1.
Chromosome analysis to look for a visible change in chromosome 13. This is likely to be normal in 95% of cases and show a deletion (missing piece) in 5% of cases.
2.
DNA or molecular genetic testing to look for the alteration or damage in the Rb gene in the affected person. This testing is technically difficult, as the Rb gene is quite large and alterations can happen anywhere in it. The location of the alteration tends to be different in different families; so the testing can take many months. It is carried out primarily by the Retinoblastoma Genetic Screening Unit (RGSU) at Bart’s Health NHS Trust and The Manchester Centre for Genomic Medicine (MCGM). The tests are not sensitive enough yet to pick up every alteration in the gene, although over 90% of altered genes can usually be found.
3.
DNA or molecular genetic testing to compare the Rb genes in the family to find out which is the altered copy of the gene without actually finding out what the alteration is. This is also called linkage analysis. It can be done only if there are at least two people with retinoblastoma in the family.
What will genetic testing show?
Testing blood samples: For people with bilateral or multifocal retinoblastoma, alterations in the Rb gene can usually be identified using blood samples.
For those with unilateral retinoblastoma, genetic testing may help to clarify which group someone is in, i.e. heritable or non-heritable. If an alteration is found in the Rb gene in blood cells this will confirm that the person has the heritable form. If an alteration is not found this may be because no alteration is present or because tests have failed to detect an alteration and therefore the results at this stage may be inconclusive. This is also true for individuals with a mosaic retinoblastoma, particularly where the gene change is only present in a small number of cells.
If an alteration cannot be found in the Rb gene in the blood cells, it may be possible for further tests to be done by examining a sample of the tumour if an eye has been removed.
Testing tumour tissue samples: Looking at the Rb gene in tumour tissue is useful both in people with bilateral retinoblastoma whose blood test has been negative and in people with unilateral retinoblastoma. This is because if alterations are found in the Rb gene in the tumour then it shows exactly what to look for in the blood, and if these alterations are not detected in the blood then it is certain that there are no alterations in the blood. In these cases it can be concluded that the retinoblastoma is non-heritable, rather than that the tests have failed to find the changes.
What is genetic counselling?
The Association of Genetic Nurses and Counsellors, the regulatory body in the UK describes the aims of genetic counselling in this way.
To help the individual or family:
- Understand information about the genetic condition.
- Appreciate the inheritance pattern and risk of recurrence.
- Understand the options available.
- Make decisions appropriate to their personal and family situation.
- Make the best possible adjustment to the disorder or risk.
For families or individuals with questions and concerns about retinoblastoma or genetic testing, genetic counselling can offer not only technical information but also help in understanding the information in relation to their own family or personal circumstances.
Have you been affected by retinoblastoma?
If you are not currently attending one of the retinoblastoma treatment centres in London or Birmingham and wish to have genetic counselling, please contact your GP and ask to be referred to a local genetics counsellor who will make arrangements for you. Alternatively you can contact either retinoblastoma centre and ask to be put in contact with their retinoblastoma genetics counsellor.