Genetic and Epigenetic Profile of Retinoblastoma in a Chinese Population: Analysis of 47 Patients
Genetic and Epigenetic Profile of Retinoblastoma in a Chinese Population: Analysis of 47 Patients
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DOI：
10.1097/apo.0000000000000016
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发表时间：
2013-11-01
影响因子：
4.4
通讯作者：
Jonas, Jost B.
中科院分区：
文献类型：
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作者：
Cheng, Guangyin;Wang, Yichen;Jonas, Jost B.
目的：报告中国人视网膜母细胞瘤基因RB1的遗传学发现。设计：回顾性非比较病例系列。方法：从外周血样本中提取基因组DNA，并收集47例患者的肿瘤组织样本（37例单侧视网膜母细胞瘤患者）。通过聚合酶链反应Y单链构象多态性YDNA测序筛选27个已知的RB1编码外显子、剪接边界和启动子是否存在点突变或小突变。对 30 名患者进行了微卫星分析，这些患者的血液样本和视网膜母细胞瘤肿瘤组织均可根据 RB1 基因座内或邻近的微卫星标记检查杂合性丢失。通过甲基化特异性聚合酶链反应，对 40 名患者的视网膜母细胞瘤组织样本中 RB1 基因的甲基化进行了研究。结果：在 10 名患者 (21%) 中鉴定出 RB1 基因突变。在 26 名患者中的 14 名中检测到 D13S153 基因座杂合性丢失，在 28 名患者中的 13 名中检测到 D13S262 基因座杂合性丢失，以及 27 名患者中的 8 名患者中的 8 名 D13S284 基因座检测到杂合性丢失。总共，30 名患者中有 18 名（60%）检测到杂合性缺失。 RB1 基因座杂合性的丧失与 pRb 表达的丧失相关（P = 0.01）。在 40 名接受检查的患者中，有 4 名 (10%) 发现 RB1 基因启动子 CpG 岛高度甲基化。 结论：在中国视网膜母细胞瘤患者中发现的突变的定位和类型与之前在其他种族群体的研究中观察到的模式非常吻合。没有发现新的突变。未来的研究可能会检验这些结果是否有助于中国患者的遗传咨询。
Purpose: To report genetic findings of retinoblastoma gene RB1 in a Chinese ethnic group with retinoblastoma.Design: A retrospective noncomparative case series.Methods: Genomic DNA was extracted from peripheral blood samples, and tumor tissue samples were collected from 47 patients (37 patients with unilateral retinoblastoma). The 27 known RB1 coding exons, splicing boundaries, and promoters were screened for point mutations or small mutations by polymerase chain reactionYsingle-strand conformation polymorphismYDNA sequencing. Microsatellite analysis was applied to 30 patients with both blood samples and retinoblastoma tumor tissues available to examine loss of heterozygosity according to microsatellite markers within or adjacent to the RB1 locus. Methylation of the RB1 gene was investigated in retinoblastoma tissue samples of 40 patients by methylation-specific polymerase chain reaction.Results: Mutations in the RB1 gene were identified in 10 patients (21%). A loss of heterozygosity was detected at locus D13S153 in 14 of 26 patients, at locus D13S262 in 13 of 28 patients, and at locus D13S284 in 8 of 27 patients. Altogether, loss of heterozygosity was detected in 18 (60%) of 30 patients. Loss of heterozygosity at the RB1 locus was associated with a loss of pRb expression (P = 0.01). Hypermethylation in the promoter CpG island in the RB1 gene was found in 4 (10%) of 40 examined patients.Conclusions: The localization and type of mutations identified in Chinese patients with retinoblastoma fit well into the pattern observed in previous studies on other ethnic groups. No new mutations were found. Future studies may examine whether these results are helpful for genetic counseling of Chinese patients.