Kuroki T, Fujiwara Y, Nakamori S, Imaoka S, Kanematsu T, Nakamura Y
Laboratory of Molecular Medicine, University of Tokyo, Japan.
Br J Cancer. 1995 Aug;72(2):383-5. doi: 10.1038/bjc.1995.342.
The concept that genetic changes accumulate during development and progression of cancer is widely accepted. Frequent allelic losses at chromosome 13q have been found in hepatocellular carcinomas (HCCs), and a known tumour-suppressor at 13q14, the retinoblastoma (RB) gene, is thought to be the target of those events. However, no strong evidence has emerged to support a significant role of RB during hepatocarcinogenesis. To investigate the minimal area(s) of loss on chromosome 13q in HCCs, we analysed DNAs isolated from 92 tumours for loss of heterozygosity (LOH) at 13 loci on chromosome 13q, using polymorphic microsatellite markers. In 30 (32.6%) of 92 cases we detected LOH for at least one locus on chromosome 13q and 20 revealed a partial or interstitial deletion of chromosome 13q. Deletion mapping of these 20 tumours indicated two separate commonly deleted regions: one was located in the region including RB and the other was located in the region including the BRCA2 locus. These findings suggest that at least one putative tumour-suppressor gene for HCC other than RB, possibly BRCA2, exists on chromosome 13q.
癌症发生发展过程中基因变化会不断累积这一概念已被广泛接受。在肝细胞癌（HCC）中发现13号染色体长臂（13q）频繁出现等位基因缺失，并且位于13q14的一个已知肿瘤抑制基因——视网膜母细胞瘤（RB）基因，被认为是这些事件的作用靶点。然而，尚未出现有力证据支持RB在肝癌发生过程中发挥重要作用。为了研究HCC中13q染色体上最小缺失区域，我们使用多态性微卫星标记分析了从92个肿瘤中分离的DNA，检测13q染色体上13个位点的杂合性缺失（LOH）。在92例病例中的30例（32.6%），我们检测到13q染色体上至少一个位点存在LOH，并且20例显示13q染色体有部分或中间缺失。对这20个肿瘤进行缺失定位表明存在两个独立的常见缺失区域：一个位于包含RB的区域，另一个位于包含BRCA2基因座的区域。这些发现提示，13q染色体上除RB外至少存在一个推测的HCC肿瘤抑制基因，可能是BRCA2。
