Narrow Results

Retinoblastoma is an embryonic neoplasm of retinal origin. Tumour development in retinoblastoma is initiated by the somatic inactivation of both alleles of the RB1 gene. It is predicted that 40% of all cases of retinoblastoma are hereditary with all bilateral and 10-15% of unilateral cases being constitutional in origin. In this study, the incidence of somatic loss of heterozygosity (LOH) as a mutational event in retinoblastoma was studied using four intragenic DNA markers. These include a microsatellite polymorphism, RB1.20 and four restriction fragment length polymorphisms (RFLPs) namely, intron 1/BamHI, intron 17/XbaI, intron 24/Tth1 III and intron 25/DraI. LOH was found in 17 out of 27 (63%) tumours analysed. A higher frequency of maternal loss compared to paternal loss was observed in bilateral cases (75%) as compared to unilateral cases (54%). Direct exon-by-exon sequencing revealed mutations in 15 out of 17 (88%) tumours with LOH. In three out of ten tumours without LOH, one mutation was detected and two mutations were found in five tumours without LOH. Seven of the mutations were found to be constitutional (germline) in origin with three of these mutations occurring in unilateral cases of retinoblastoma. The presence of constitutional mutations did not correlate with early age of tumour development. Our results show that there was no association between the types of mutation and constitutional origin of the mutation.