Improved clinical management of retinoblastoma through gene testing.

Aims: To investigate the relative benefits of retinoblastoma gene testing over conventional ophthalmological screening methods in a New Zealand setting, and to determine the importance of tumour material in resolving germline status.

Methods: Three cases of gene testing are described to illustrate the clinical advantages over conventional ophthalmological screening. To determine the role of tumour material in resolving germline status, 24 New Zealand families were tested, of which tumour material was available for eight.

Results: In the three cases reported, we found genetic testing of the RB1 gene resulted in clinically significant benefits and cost savings. When fresh tumour was available for high molecular weight DNA extraction, germline status was resolved in 8/8 (100%) cases. In these cases tumour mutations were not present in the corresponding peripheral blood DNA, indicating that the tumours were sporadic. In the absence of tumour DNA, mutations were identified in only 8/13 (62%) heritable cases. Germline status remains unresolved in all of the three cases of unilateral tumour without a family history or tumour DNA.

Conclusions: Our experience indicates that retinoblastoma gene testing has significant benefits to the affected individuals and their families in New Zealand. Moreover, DNA extracted from fresh tumour allows retinoblastoma germline status in most cases to be defined. Without rumour material, the germline status of potentially sporadic cases will remain undetermined since the absence of detectable RB1 coding region mutations does not exclude all possible mutations in the RB1 gene, which is too large for DNA analysis. A lack of conclusive results will mean that infants will be subjected to the unnecessary inconvenience of surveillance under general anaesthesia.