Ohtsu K, Hiyama E, Ichikawa T, Matsuura Y, Yokoyama T
First Department of Surgery and Department of General Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan.
Clin Cancer Res. 1997 Jul;3(7):1221-8.
Several loci on the short arm of chromosome 1 (1p) have been reported as the consensus deleted regions for the putative suppressor genes of neuroblastoma by deletion mapping. The significance of deletion in 1p on the clinical features of neuroblastoma remains controversial. To clarify the relationship between the clinical features of neuroblastoma cases and genetic status of 1p, we performed deletion mapping on 1p on samples obtained from 58 cases with neuroblastoma using 12 highly polymorphic microsatellite or minisatellite loci. Loss of heterozygosity of 1p was detected in 19 cases (33%) of primary tumors and in 21 cases (36%) when metastatic and recurrent sites were included. They were classified into two groups according to the 1p deletion pattern: interstitial deletion (group I, n = 11) and terminal deletion (group T, n = 10). The shortest region of overlap in group I ranged between FGR and D1S170 (1p36.1-2). Clinically, all group I cases survived disease free, and none of these cases showed MYCN amplification. However, in group T, eight (80%) cases showed a large terminal deletion from D1S162 (1p32-pter), including the shortest region of overlap of group I, and two (20%) showed a very terminal deletion from D1S160 (1p 36.3). Of the group T cases, only two survived disease free, and seven (70%) showed MYCN amplification. Thus, the candidates for the locations of neuroblastoma suppressor genes on 1p may involve at least two regions, which demonstrate different clinical features.
通过缺失定位，1号染色体短臂（1p）上的几个位点已被报道为神经母细胞瘤假定抑癌基因的一致性缺失区域。1p缺失对神经母细胞瘤临床特征的意义仍存在争议。为了阐明神经母细胞瘤病例的临床特征与1p基因状态之间的关系，我们使用12个高度多态性的微卫星或小卫星位点，对58例神经母细胞瘤患者的样本进行了1p缺失定位。在19例（33%）原发性肿瘤中检测到1p杂合性缺失，若包括转移和复发部位，则在21例（36%）中检测到。根据1p缺失模式将它们分为两组：间质缺失（I组，n = 11）和末端缺失（T组，n = 10）。I组最短重叠区域在FGR和D1S170之间（1p36.1 - 2）。临床上，所有I组病例均无病存活，且这些病例均未显示MYCN扩增。然而，在T组中，8例（80%）显示从D1S162（1p32 - pter）开始的大片末端缺失，包括I组最短重叠区域，2例（20%）显示从D1S160（1p36.3）开始的极末端缺失。在T组病例中，只有2例无病存活，7例（70%）显示MYCN扩增。因此，1p上神经母细胞瘤抑癌基因的候选位置可能至少涉及两个区域，这两个区域表现出不同的临床特征。
