Fung Y K, Murphree A L, T'Ang A, Qian J, Hinrichs S H, Benedict W F
Science. 1987 Jun 26;236(4809):1657-61. doi: 10.1126/science.2885916.
The retinoblastoma (Rb) gene is the prototype for a class of recessive human cancer genes in which loss of activity of both normal alleles is thought to be associated with tumorigenesis. Sixteen of 40 retinoblastomas examined with a complementary DNA probe shown to be the Rb gene had identifiable structural changes of the Rb gene including in some cases homozygous internal deletions with corresponding truncated transcripts. An osteosarcoma also had a homozygous internal deletion with a truncated transcript. In addition, possible hot spots for deletion were identified within the Rb genomic locus. Among those tumors with no identifiable structural changes there was either absence of an Rb transcript or abnormal expression of the Rb transcript. Comparison of the structural changes in the tumor cells and fibroblasts of certain patients provided support for Knudson's two-hit hypothesis for the development of retinoblastoma at the molecular level. The ability to detect germline structural deletions in fibroblasts from some patients with bilateral retinoblastoma also indicates that the isolated gene is useful for diagnostic purposes.
视网膜母细胞瘤（Rb）基因是一类隐性人类癌症基因的原型，其中两个正常等位基因活性的丧失被认为与肿瘤发生有关。用一种被证明是Rb基因的互补DNA探针检测的40个视网膜母细胞瘤中，有16个具有可识别的Rb基因结构变化，包括在某些情况下的纯合内部缺失及相应的截短转录本。一个骨肉瘤也有一个带有截短转录本的纯合内部缺失。此外，在Rb基因组位点内确定了可能的缺失热点。在那些没有可识别结构变化的肿瘤中，要么没有Rb转录本，要么Rb转录本表达异常。某些患者肿瘤细胞和成纤维细胞结构变化的比较，在分子水平上为Knudson关于视网膜母细胞瘤发生的双击假说提供了支持。检测一些双侧视网膜母细胞瘤患者成纤维细胞中种系结构缺失的能力也表明，分离出的该基因可用于诊断目的。
