Background/aims: Loss of heterozygosity (LOH) has been discovered in retinoblastoma (RB) in previous studies. In this study we aimed to discover potential tumour suppressor genes through investigation of the incidence of allelic loss in chromosome 1, 6, 9, 13, 19, 20, 21, 22 and X in Chinese sporadic retinoblastoma patients and to study the expression of genes flanking LOH region 13q31.
Methods: Twenty-five microdissected RB samples were analyzed to investigate the LOH in 140 microsatellite markers. Expression of genes flanking D13S265 was investigated by real-time quantitative-PCR on available frozen samples. The promoter and entire coding region of GPC6 were examined for sequence changes in an extended batch of 29 RB samples.
Results: Allele losses were found in 92% (23/25) of the tumors. We identified a new LOH locus at 13q31 (D13S265) with high ocurrence rate (67%, 14/21) apart from the RB1 locus (68%, 17/25). Expression study detected the reduced expression of Glypican 6 (GPC6) transcript is significantly associated with the LOH at 13q31 (p=0.024). Furthermore, mutation screening revealed no remarkable sequence alteration in GPC6 that could affect its expression.
Conclusion: Our result document that reduction of GPC6 mRNA in retinoblastoma is associated with the non-random allelic loss at 13q31 that could contribute to RB development.