Mosaic retinoblastoma means a fraction of cells in the whole body carry one mutated copy of the RB1 gene.
Each cell also carries one normal copy of the RB1 gene. The rest of the cells carry two normal copies of RB1.
Mosaicism is a form of heritable RB1-/- retinoblastoma that cannot be inherited because it only happens at or after conception.
Imagine a two cell embryo. Each of the two cells has two normal copies of RB1. In the process of cell division, one copy of the gene in one cell somehow becomes damaged.
Now there are four cells, but one carries a mutated copy of the RB1 gene. Those four cells then divide to become eight cells – two carrying a mutated copy of RB1, and six undamaged. When the eight cells divide to become sixteen, four will have a damaged copy of RB1, and 12 will be undamaged. So the process continues.
When the baby is born, 25% of his cells will carry a mutated copy of RB1 and one normal copy of the gene. The other 75% of cells will carry two normal copies.
For retinoblastoma to develop, the other copy RB1 must also become mutated in a retinal cell where one copy of the gene is already damaged.
Risk for Retinoblastoma
Mosaicism can happen in both boys and girls, and children with a mosaic mutation can have retinoblastoma. Theoretically, the lower the fraction of affected cells, the lower the risk of developing retinoblastoma. Many children with a mosaic mutation develop cancer in only one eye.
If the gonad (egg or sperm cell) has an RB1 mutation, the baby will carry that mutation in every cell, and will most likely develop tumours in both eyes.
If genetic testing finds the child has a mosaic RB1 mutation, parents and siblings are not at risk, since mosaicism cannot be inherited. However, offspring of the affected child will have a risk for inheriting the mutation, which would be present in all cells of the body.
Testing and Research
Some technologies can detect low level RB1 mutations, particularly PCR for the precise mutation. PCR (polymerase chain reaction) makes millions of copies of a known piece of DNA. If the fraction of cells with the RB1 mutation is very small, testing blood with many technologies will not see the mutation.
Mosaicism of RB1 was first shown at Retinoblastoma Solutions (now Impact Genetics) in Toronto, the world’s only lab dedicated solely to RB1 genetic testing and research. The demonstrated rate for mosaicism at Impact Genetics is about 8%, though the incidence is a little higher, since very low level mosaicism cannot currently be detected.