McDonald J D, Daneshvar L, Willert J R, Matsumura K, Waldman F, Cogen P H
Department of Neurological Surgery, University of California, San Francisco 94143.
Genomics. 1994 Sep 1;23(1):229-32. doi: 10.1006/geno.1994.1481.
Deletion mapping of a medulloblastoma tumor panel revealed loss of distal chromosome 17p13.3 sequences in tumors from 14 of 32 patients (44%). Of the 14 tumors showing loss of heterozygosity by restriction fragment length polymorphism analysis, 14 of 14 (100%) displayed loss of the telomeric marker p144-D6 (D17S34), while a probe for the ABR gene on 17p13.3 was lost in 7 of 8 (88%) informative cases. Using pulsed-field gel electrophoresis, we localized the polymorphic marker (VNTR-A) of the ABR gene locus to within 220 kb of the p144-D6 locus. A cosmid contig constructed in this region was used to demonstrate by fluorescence in situ hybridization that the ABR gene is oriented transcriptionally 5' to 3' toward the telomere. This report provides new physical mapping data for the ABR gene, which has not been previously shown to be deleted in medulloblastoma. These results provide further evidence for the existence of a second tumor suppressor gene distinct from p53 on distal chromosome 17p.
对一组髓母细胞瘤肿瘤样本进行缺失图谱分析发现，32例患者中有14例（44%）的肿瘤出现17号染色体短臂13.3远端序列缺失。在通过限制性片段长度多态性分析显示杂合性缺失的14个肿瘤中，14个（100%）均显示端粒标记p144-D6（D17S34）缺失，而在8个信息充分的病例中，17p13.3上ABR基因的一个探针在7个（88%）病例中缺失。使用脉冲场凝胶电泳，我们将ABR基因座的多态性标记（VNTR-A）定位到距p144-D6基因座220 kb范围内。利用该区域构建的黏粒重叠群，通过荧光原位杂交证明ABR基因转录方向为5'至3'朝向端粒。本报告提供了ABR基因新的物理图谱数据，此前尚未发现该基因在髓母细胞瘤中发生缺失。这些结果进一步证明在17号染色体短臂远端存在一个不同于p53的第二个肿瘤抑制基因。
