[Genetic and molecular diagnostics in retinoblastoma]

Retinoblastoma is a childhood malignancy of the eye. Almost all patients with familial or bilateral disease suffer from the hereditary form of the disease that is caused by germline mutations in one allele of the RB1 gene. Tumor development is initiated by the loss of the second RB allele in a retinal progenitor cell. Most patients with isolated unilateral disease have nonhereditary retinoblastoma and thus do not carry a mutant allele in their germline. In no patient, the presence of a germline mutation can be excluded clinically. Consequently, relatives are at an increased risk for retinoblastoma. Molecular testing, however, enables accurate risk prediction provided that samples are available. In some relatives an increased risk can be excluded by segregation analysis. Most often, however, identification of the disease causing mutation is necessary for accurate risk prediction. Mutation analysis, which is impeded by the size and complexity of the RB gene, is facilitated by use of efficient screening methods. Using these methods, the oncogenic mutation can be identified in most patients. Therefore, predictive testing has become an integral part of contemporary management of retinoblastoma.