Friend S H, Bernards R, Rogelj S, Weinberg R A, Rapaport J M, Albert D M, Dryja T P
Nature. 1986;323(6089):643-6. doi: 10.1038/323643a0.
The genomes of various tumour cells contain mutant oncogenes that act dominantly, in that their effects can be observed when they are introduced into non-malignant cells. There is evidence for another class of oncogenes, in which tumour-predisposing mutations are recessive to wild-type alleles. Retinoblastoma is a prototype biological model for the study of such recessive oncogenes. This malignant tumour, which arises in the eyes of children, can be explained as the result of two distinct genetic changes, each causing loss of function of one of the two homologous copies at a single genetic locus, Rb, assigned to the q14 band of human chromosome 13. Mutations affecting this locus may be inherited from a parent, may arise during gametogenesis or may occur somatically. Those who inherit a mutant allele at this locus have a high incidence of non-ocular, second tumours, almost half of which are osteosarcomas believed to be caused by the same mutation. Here we describe the isolation of a complementary DNA segment that detects a chromosomal segment having the properties of the gene at this locus. The gene is expressed in many tumour types, but no RNA transcript has been found in retinoblastomas and osteosarcomas. The cDNA fragment detects a locus spanning at least 70 kilobases (kb) in human chromosome band 13q14, all or part of which is frequently deleted in retinoblastomas and osteosarcomas.
各种肿瘤细胞的基因组都含有呈显性作用的突变致癌基因，也就是说，当将它们导入非恶性细胞时，其作用就能被观察到。有证据表明还存在另一类致癌基因，其中的肿瘤易感性突变相对于野生型等位基因是隐性的。视网膜母细胞瘤是研究此类隐性致癌基因的一个典型生物学模型。这种发生于儿童眼部的恶性肿瘤，可以解释为是两种不同基因变化的结果，每种变化都会导致位于人类13号染色体q14带的单一基因座Rb上的两个同源拷贝之一功能丧失。影响该基因座的突变可能从父母一方遗传而来，可能在配子发生过程中出现，也可能在体细胞中发生。那些在该基因座遗传了一个突变等位基因的人，发生非眼部第二肿瘤的几率很高，其中近一半是骨肉瘤，据信是由同一突变引起的。在此，我们描述了一个互补DNA片段的分离，该片段可检测到具有该基因座基因特性的一个染色体片段。该基因在多种肿瘤类型中都有表达，但在视网膜母细胞瘤和骨肉瘤中未发现RNA转录本。该cDNA片段检测到人类13号染色体带13q14中一个跨度至少为70千碱基（kb）的基因座，在视网膜母细胞瘤和骨肉瘤中，该基因座的全部或部分经常缺失。
