Sarcoma and familial retinoblastoma

Retinoblastoma is the most common malignant ocular tumour of childhood. It results from mutations in the retinoblastoma gene, RB1, which may be sporadic or heritable. Only 10-25% of patients have a family history of retinoblastoma and can be assumed to have a heritable RB1 mutation. A small proportion of the remaining patients may have a heritable mutation despite the lack of relatives with retinoblastoma. Heritable RB1 mutations are associated with an increased risk of sarcoma. Described herein are three patients with a past history of retinoblastoma, no family history of retinoblastoma, and a first-degree relative with sarcoma. Mutation analyses were performed on DNA samples from these patients to test for heritable RB1 mutations.

A genomic DNA analysis of RB1 gene.

Heritable mutations in the RB1 gene were identified in two of the three cases. In these two cases, Bayesian risk calculation indicated that the chance of the affected relatives having the familial RB1 mutation was greater than 90%. In the case without an identified mutation, Bayesian risk analysis indicated that the chance of there being an unidentified familial RB1 mutation was low (16%) but could still be clinically significant in managing the family.

The risk of non-ocular malignancies and the availability of genetic testing for heritable RB1 mutations have important clinical implications for the management of children with retinoblastoma.