About Retinoblastoma Genetics
Jump to Questions Asked by Retinoblastoma Families
Retinoblastoma and the RB1 Gene
Benefits of RB1 Genetic Testing
Testing Unilaterally Affected Individuals when there is no Tumor DNA
How our Tests Work
Retinoblastoma and the RB1 Gene
- Retinoblastoma is the most common childhood eye cancer. Except for germ cells (ova and sperm), each
healthy cell in our bodies carries two copies of the RB1 gene, one inherited from the mother and one
from the father.
- Retinoblastoma tumors grow either because both the paternal and maternal copies of the RB1 gene
in a cell are mutated or because one copy is mutated and the second copy is lost (called loss of
heterozygosity).
- A mutation copied in germ cells (ova or sperm) is called a germline mutation. A mutation that occurs
after the retina forms, and is not carried in germ cells, is called a somatic mutation.
- Each child born to an individual who carries a germline RB1 mutation has a 50% chance to inherit
the tendency to develop retinoblastoma. An individual who carries a somatic RB1 gene mutation
may have retinoblastoma, but cannot pass the tendency to develop retinoblastoma to his or her children.
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Benefits of RB1 Genetic Testing
For a
bilaterally affected individual, genetic testing in our lab identifies the unique
RB1 gene mutation
(with 92% probability) that led to his or her retinoblastoma. This knowledge means that:
- the proband's parents can be tested for the proband's RB1 gene mutation.
One of the parents can carry the proband's RB1 gene mutation and not have retinoblastoma. An adult carrier is
at risk of secondary tumors and each child of an adult carrier is at risk of retinoblastoma.
- infant brothers, sisters, and cousins can be tested for the proband's mutation.
Children who carry the proband's mutation need frequent clinic exams; early identification of tumors saves vision,
eyes and lives. Children proven not to carry the proband's mutation are at population risk and can be removed safely from
clinical surveillance.
For a
unilaterally affected individual, if DNA from fresh or frozen tumor tissue can be studied along with
DNA from blood, genetic testing in our lab identifies each of two
RB1 gene mutations that led to tumor(s), with
90% probability.
This knowledge allows relatives at risk to be tested and determines:
- whether the individual has a heritable form (15% prior probability) of
retinoblastoma or not (85% prior probability).
- whether or not the individual is at lifelong risk of secondary tumors like osteosarcoma.
- whether the individual's own (future) children will be at risk of inheriting retinoblastoma.
Testing Unilaterally Affected Individuals when there is no Tumor DNA
Even when
no fresh or frozen tumor tissue can be studied for a
unilaterally affected individual,
genetic testing of DNA from blood alone:
- identifies a germline RB1 gene mutation for 13.5% of cases, and
- reduces the remaining risk of a germline mutation from 15% to 1.5%
Benefits to Adult Survivors
For an adult retinoblastoma survivor whose
RB1 mutation is identified, genetic testing also means that:
- each of the proband's children can be tested.
- rapid pre-natal testing is feasible.
Parents and doctors can plan in advance how to treat the tumors of babies who carry a parent's mutation, including the
possibility of inducing early delivery at 36 weeks' gestation while tumors are quite small.
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