Toguchida J, Ishizaki K, Sasaki M S, Nakamura Y, Ikenaga M, Kato M, Sugimot M, Kotoura Y, Yamamuro T
Radiation Biology Center, Faculty of Medicine, Kyoto University, Japan.
Nature. 1989 Mar 9;338(6211):156-8. doi: 10.1038/338156a0.
Successive loss of function of both alleles of the retinoblastoma susceptibility gene (RB) on human chromosome 13 seems to be critical in the development of retinoblastoma and osteosarcoma. In cases where the tumour is familial and susceptibility is inherited, a mutation in one of the alleles is carried in the germline. We have recently shown that cytogenetically visible germline mutations are usually in the paternally derived gene. Such a bias would not be expected for sporadic (non-familial) tumours, where both mutations occur in somatic tissue, but there has been some indication of a bias towards initial somatic mutation in the paternally derived gene on chromosome 11 in sporadic Wilms tumour. We have now examined 13 sporadic osteosarcomas and find evidence which indicates that in 12 cases the initial mutation was in the paternal gene, suggesting the involvement of germinal imprinting in producing the differential susceptibility of the two genes to mutation.
人类13号染色体上视网膜母细胞瘤易感基因（RB）的两个等位基因功能的相继丧失，似乎在视网膜母细胞瘤和骨肉瘤的发生发展中起关键作用。在肿瘤为家族性且易感性可遗传的情况下，一个等位基因的突变存在于种系中。我们最近发现，细胞遗传学上可见的种系突变通常存在于父源基因中。对于散发性（非家族性）肿瘤，两个突变都发生在体细胞组织中，这种偏向性是不会出现的，但有迹象表明，散发性肾母细胞瘤中11号染色体上父源基因的初始体细胞突变存在偏向性。我们现在检查了13例散发性骨肉瘤，发现有证据表明，在12例中初始突变存在于父源基因中，这表明生殖印记参与了导致这两个基因对突变的易感性差异。
