Abstract

Background: Retinoblastoma is the most common intraocular malignancy in childhood and is responsible for approximately 1% of all deaths caused by childhood cancer.

Aims/methods: Comparative genomic hybridisation was performed on 13 consecutive, histologically confirmed retinoblastomas to analyse patterns of chromosomal changes and correlate these to clinicopathological variables. Six cases were hereditary and seven cases were sporadic.

Results: In 11 of the 13 tumours chromosomal abnormalities were detected, most frequently gains. Frequent chromosomal gains concerned 6p (46%), 1q (38%), 2p, 9q (30%), 5p, 7q, 10q, 17q, and 20q (23%). Frequent losses occurred at Xq (46%), 13q14, 16q, and 4q (23%). High level copy number gains were found at 5p15 and 6p11–12. A loss at 13q14 occurred in three cases only. Relatively few events occurred in the hereditary cases (27) compared with the non-hereditary cases (70 events). The number of chromosomal aberrations in these 13 retinoblastomas showed a bimodal distribution. Seven tumours showed less than four chromosomal aberrations, falling into a low level chromosomal instability (CIN) group, and six tumours showed at least eight aberrations, falling into a high level CIN group. In the low level CIN group the mean age was half that seen in the high level CIN group, there were less male patients, and there were more hereditary and bilateral cases. Microsatellite instability was not detected in either of the two groups.

Conclusion: Despite the complex pattern of genetic changes in retinoblastomas, certain chromosomal regions appear to be affected preferentially. On the basis of the number of genetic events, retinoblastomas can be divided in low and a high level chromosomal instability groups, which have striking differences in clinical presentation.