Reissmann P T, Simon M A, Lee W H, Slamon D J
Department of Medicine, UCLA School of Medicine.
Oncogene. 1989 Jul;4(7):839-43.
The retinoblastoma susceptibility gene, (RB), is a tumor suppressor gene which, when deleted is associated with the development of retinoblastoma. The observation that children with heritable retinoblastoma frequently develop second malignancies, principally sarcomas, led to the detection of similar RB gene deletions in some osteosarcomas. We studied 44 unselected sarcomas from patients with no antecedent retinoblastoma to determine the prevalence and nature of RB gene alterations. DNA and RNA were extracted from fresh tumors and analysed by Southern and Northern blotting. Three of nine osteosarcomas and 4 of 29 soft-tissue sarcomas had deletions of the RB gene. Four of these were full-length, and three were partial deletions of the gene. RNA from 5 of the 7 deleted tumors was studied, and 4 cases completely lacked the RB transcript. Transcripts were found in 19 of 20 tumors with an apparently intact RB gene, and in all the normal tissues studied. An additional tumor lacked the RB transcript, but the gene appeared intact at the DNA level. In total, 8 of 38 sarcomas were found to have alterations of the RB gene. These data indicate that the RB gene is inactivated in a significant number of sarcomas unrelated to retinoblastoma, and that the potential role for the gene in the pathogenesis of human malignancy may not be limited to retinoblastoma.
视网膜母细胞瘤易感基因（RB）是一种肿瘤抑制基因，该基因缺失时与视网膜母细胞瘤的发生相关。患有遗传性视网膜母细胞瘤的儿童经常发生第二种恶性肿瘤，主要是肉瘤，这一观察结果导致在一些骨肉瘤中检测到类似的RB基因缺失。我们研究了44例无视网膜母细胞瘤病史患者的未选择的肉瘤，以确定RB基因改变的发生率和性质。从新鲜肿瘤中提取DNA和RNA，并通过Southern印迹法和Northern印迹法进行分析。9例骨肉瘤中有3例，29例软组织肉瘤中有4例存在RB基因缺失。其中4例为全长缺失，3例为基因部分缺失。对7例缺失肿瘤中的5例的RNA进行了研究，4例完全缺乏RB转录本。在20例RB基因明显完整的肿瘤中有19例发现了转录本，在所研究的所有正常组织中也发现了转录本。另有一个肿瘤缺乏RB转录本，但该基因在DNA水平上似乎是完整的。总共38例肉瘤中有8例被发现存在RB基因改变。这些数据表明，RB基因在大量与视网膜母细胞瘤无关的肉瘤中失活，并且该基因在人类恶性肿瘤发病机制中的潜在作用可能不限于视网膜母细胞瘤。
