视网膜母细胞瘤中基因杂合缺失现象的研究

目的：由于Rb1基因的失活可能不是引发视网膜母细胞瘤（RB）的唯一因素。因此，此项课题中我们通过探索第13号染色体上基因杂合缺失（LOH）现象发生的机率以及通过家系分析确定标记位点缺失的遗传学源，试图探明其它可能参与RB发生发展的基因存在的位点，并试图寻找和确定具有诊断及预后价值的LOH检测指标。方法：16个RB患者成对的肿瘤与其相应血清标本在13号染色体上14个微卫星标记处通过荧光PCR进行扩增，分别测定LOH；并通过对患者家庭进行分析确定标记位点缺失的遗传学来源。结果：16个RB患者上，12个在13号染色体上一个或一个以上位点发生LOH，其中三个位点，D13S265，D13S263和D13S153（位于Rb1基因内），LOH发生机率最高，分别是8个，8个和9个，12个LOH阳性标本中有10个标记位点的缺失被确定发生在父系来源的染色体中，LOH阳性及阴性组肿瘤的发生时间分别为504d和1086d。结论：在位点D13S263（13q14.1-14.2)和D13S265（13q31-32)处可能含有某些未知基因参与RB的发生发展，在我们的实验群体中标记位点缺失大多选择性地发生在父系来源的染色体中，此外，LOH阳性组的患者RB确诊时间早于LOH阴性组，其中D13S263和D13S265两个位点的LOH现象可能对RB的早期诊断具有一定提示作用。

Studies on loss of heterzygosity in retinoblastoma

Objective To identify the specific loci containing suspected genes which might play roles in the onset or progress of retinoblastoma (RB) by investigating the incidence of loss of heterozygosity (LOH) on chromosome 13 and the parental origin of deletion with linkage analysis, and to explore the diagnostic and prognostic significance of LOH at specific loci. Methods Paired blood and RB tumor samples from 16 patients were analyzed with fluorescent PCR for LOH at 14 microsatellite marker loci on chromosome 13. Linkage analyses were also performed to identify the parental origin of deletion. Results Of the 16 patients, 12 had LOH at one or more loci. Three markers, D13S265, D13S263 and D13S153 (within Rb1 ), showed the highest incidence of LOH, i.e. 8/12, 8/12 and 9/12 respectively. Ten of 12 LOH cases showed the preferential loss of paternal alleles. The ages when diagnosis was made in LOH and non LOH cases were 504 and 1 086 d respectively. Conclusions Loci D13S263 (13q14.1 14.2) and D13S265 (13q31 32) might contain some unidentified genes related to the tumorigenesis of RB. Most cases in our study showed the preferential loss of paternal alleles. In addition, the age when diagnosis was made was significantly lower in patients with LOH than in those without LOH, and LOH at D13S263, and D13S265 might be used as one of diagnostic indicators at an early age. More data are needed to confirm our findings.