视网膜母细胞瘤染色体基因组不稳定性的分析

目的研究视网膜母细胞瘤（RB）肿瘤细胞基因组的遗传学改变及其位点所在基因组区域。方法以每例患者的外周血基因组为正常对照，采用基因杂合缺失（LOH）和微卫星不稳定（MSI）方法分析15例RB患者激光显微采样肿瘤细胞19、20、21、22 和X染色体上55个微卫星位点的基因组不稳定现象。结果15例患者中，有10例（67%）在5条染色体的一个或多个位点上表现为基因组不稳定［LOH和(或)MSI］，其中，染色体19（33%）和20（37%）的等位基因丢失频率高于其它染色体，D19S902和D19S571间区域的高频LOH现象提示，19q13 区可能与视网膜肿瘤发生相关。根据 MSI 结果可划分出一个或多个位点发生MSI的RB亚群。结论首次提供了RB染色体19和20的LOH证据，并进一步证实了基因组不稳定在RB肿瘤发生学中具有重要作用。(中华眼底病杂志,2005,21:28-31)

Analysis of genetic instability of chromosome 19, 20, 21, 22 and X in retinoblastoma

Objective To explore the presence of common genetic alterations in retinoblastoma and to localize the altered genomic regions. Methods Genetic instability of chromosome 19, 20, 21, 22 and X of 15 microdissected retinoblastoma tumors were analyzed by the loss of heterozygosity (LOH) and microsatellite instability (MSI). Results Among the 15 patients with retinoblastoma, genome instability [LOH and(or) MSI] at one or more loci on the 5 chromosomes in 10 (67%), in which the loss of a single allele was more frequent in chromosomes 19 (33%) and 20 (27%) than in the other 3 chromosomes. High-frequency LOH between D19S902 and D19S571 suggested gene loci in the 19q13 region might be associated with tumor development in retina. According to the result of MSI, MSI occured at least in one subset of retinoblastoma. Conclusions Our results provide first evidence of LOH in chromosomes 19 and 20 in retinoblastoma and further support the presence of genome instability in retinoblastoma that may play an important role in the tumorigenesis or progression of retinoblastoma.