Retinoblastoma is caused by a mutation – or change – in the RB1 gene. This gene encodes the RB protein, which is an important element in cell regulation. This protein prevents damaged genetic information from being further replicated in our cells, representing a protective mechanism in our body. However, if the gene is altered, the protein will no longer be produced correctly or not be produced at all and will therefore be unable to carry out its function, thereby leading to the development of tumors.
Around 40% of patients have a hereditary form of retinoblastoma. Every gene is present twice in our body, meaning that we have two alleles per gene. These patients carry only one mutated allele of the RB1 gene and are therefore heterozygous. In 80% of cases, this mutation comes from a new mutation – called a de novo mutation – which occured in the mother’s ovum or the father’s sperm. For retinoblastoma to develop, however, both alleles of the RB1 gene need to be mutated. Whenever the first mutation is already present, a second mutation occurs in the retinal precursor cells in around 95% of cases, meaning that the second allele of the RB1 gene is mutated as well, causing a retinoblastoma to develop.
Retinoblastoma is inherited as an autosomal-dominant disease, where the mutation of one allele is inherited from one parent and the mutation of the other allele, in the retinal precursor cells, develops spontaneously.