Cowell J K, Cragg H
Department of Neurosciences, Cleveland Clinic Foundation, OH 44195, USA.
Eur J Cancer. 1996 Sep;32A(10):1749-52. doi: 10.1016/0959-8049(96)00201-8.
The 'two-hit' hypothesis for the development of the childhood eye cancer, retinoblastoma (Rb), predicts that bilaterally affected individuals will carry germline mutations. The second suggestion is that patients with early presentation of unilateral tumours also carry predisposing mutations. We have used SSCP analysis to study the 27 individual exons of the RB1 gene in constitutional DNA from 3 patients whose tumours were treated under the age of 12 months. Bandshifts on SSCP gels were detected in 2 of these patients which, on sequencing, were shown to be a C-->T transition converting a CGAarg to a TGAstop codon in exon 17 and an 8 bp deletion in exon 20 resulting in a downstream stop codon. The mutations seen in these patients are reminiscent of those seen in patients with hereditary Rb and confirms that at least some early onset unilateral cases carry constitutional mutations, which has important implications for genetic screening and counselling of these individuals.
儿童眼癌视网膜母细胞瘤（Rb）发生的“双打击”假说预测，双侧受累个体将携带种系突变。第二种观点认为，单侧肿瘤早期发病的患者也携带易感突变。我们使用单链构象多态性（SSCP）分析研究了3例12个月龄前接受肿瘤治疗患者的体质DNA中RB1基因的27个独立外显子。在其中2例患者的SSCP凝胶上检测到条带迁移，测序显示，其中1例为第17外显子中CGA精氨酸突变为TGA终止密码子的C→T转换，另1例为第20外显子中8 bp缺失导致下游出现终止密码子。这些患者中发现的突变让人联想到遗传性Rb患者中所见的突变，并证实至少一些早发性单侧病例携带体质突变，这对这些个体的基因筛查和遗传咨询具有重要意义。
