Dryja T P, Mukai S, Petersen R, Rapaport J M, Walton D, Yandell D W
Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
Nature. 1989 Jun 15;339(6225):556-8. doi: 10.1038/339556a0.
Retinoblastoma and osteosarcoma arise from cells that have lost both functional copies of the retinoblastoma gene. Using the cloned retinoblastoma gene and other linked polymorphic loci, it is possible to reconstruct the sequential loss of the two homologous gene copies that precedes the development of these tumours. In non-hereditary tumours, the loss of each of the two homologues occurs somatically; in hereditary cases, the initial mutation is in the germline. Recently, Toguchida et al. reported that the paternally derived copy is preferentially the first one to become mutant during the genesis of non-hereditary osteosarcomas. We report here a similar analysis of patients with retinoblastoma in which we find no such predilection for initial somatic mutations. In contrast, when an initial mutation was a new germline mutation, it was derived from the father, a result which is consistent with new germline mutations arising primarily during spermatogenesis.
视网膜母细胞瘤和骨肉瘤起源于那些已丢失视网膜母细胞瘤基因两个功能拷贝的细胞。利用克隆的视网膜母细胞瘤基因和其他连锁的多态性位点，有可能重建在这些肿瘤发生之前两个同源基因拷贝的相继丢失情况。在非遗传性肿瘤中，两个同源物中每一个的丢失都发生在体细胞中；在遗传性病例中，初始突变发生在种系中。最近，Toguchida等人报告说，在非遗传性骨肉瘤发生过程中，父源拷贝优先成为第一个发生突变的拷贝。我们在此报告对视网膜母细胞瘤患者的类似分析，我们发现初始体细胞突变不存在这种偏好。相反，当初始突变是一个新的种系突变时，它来自父亲，这一结果与主要在精子发生过程中出现的新种系突变一致。
