Retinoblastoma: a prototypic hereditary neoplasm.
Retinoblastoma: a prototypic hereditary neoplasm.
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视网膜母细胞瘤：一种原型遗传性肿瘤。
DOI：
10.5555/uri:pii:0093775478900209
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发表时间：
1978
影响因子：
4
通讯作者：
A. Knudson
中科院分区：
文献类型：
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作者：
A. Knudson
虽然视网膜母细胞瘤是一种相对罕见的肿瘤，但它以遗传性和非遗传性的形式存在，其快速生长和易于检测使其成为研究癌症起源的有用模型。从这项研究得出的结论是，遗传性和非遗传性的这种肿瘤，可能还有其他许多肿瘤，都是由类似的过程产生的，对遗传形式的研究有助于我们对癌症的总体理解。视网膜母细胞瘤有单侧和双侧两种形式。现在有足够多的这种肿瘤的幸存者证实了这样的说法，即双侧受累个体的后代面临大约50%的风险，正如预期的那样，显性遗传性疾病。相比之下，只有10%-15%的单方面受影响的人的后代面临这样的风险。然而，当双侧病例的后代受到影响时，他们可能患有单侧肿瘤，单侧病例的后代也可能患有单侧肿瘤。因此，并不是一些家系携带双侧肿瘤的高渗透基因和一些单侧肿瘤的低渗透基因，而是双侧病例总是与生殖细胞获得性突变有关，而只有一小部分单侧病例受到这种影响。据估计，60%的病例是非遗传性的，40%是遗传性的。许多所谓的遗传性病例以前没有视网膜母细胞瘤的家族史，应该强调的是，没有这种家族史的受影响个体在大多数情况下是新的生发突变的产物。视网膜母细胞瘤基因携带者主要获得双侧肿瘤，但有时仅获得单侧肿瘤。事实上，即使父母和孩子有一个或多个肿瘤，也有一些人没有患上肿瘤。在这种情况下，似乎可以肯定的是，个体携带了基因，但没有受到影响。不发生肿瘤的基因携带者的确切比例尚不清楚，但约为5%的数量级。在另一种极端情况下，有些人不仅双眼有肿瘤，而且一只眼有几个原发肿瘤。基因携带者获得的肿瘤数量似乎是，
A LTHOUGH RETINOBLASTOMA is a relatively rare tumor, its existence in both hereditary and nonhereditary forms, its rapid growth, and its ease of detection make it useful as a model for the study of the origin of cancer. From such a study it is concluded that the hereditary and nonhereditary forms of this, and probably many other, tumors arise by similar processes and that the study of hereditary forms can contribute to our understanding of cancer generally. Retinoblastoma occurs in both unilateral and bilateral forms. There are now enough survivors of this tumor to substantiate the claim that the offspring of bilaterally affected individuals are at approximately 50% risk, as expected for a dominantly inherited condition. By contrast the offspring of only lo%-15% of unilaterally affected individuals are at such risk. Yet when the offspring of bilateral cases are affected they may have unilateral tumor, and vice versa for the offspring of unilateral cases. It is therefore not that some families carry a highly penetrant gene for bilateral tumors and some a lowly penetrant gene for unilateral tumor, but rather that bilateral cases are always associated with a germinally acquired mutation while only a minor fraction of unilateral cases are so affected. One estimate is that 60% of all cases are nonhereditary and 40% are hereditary.’ Many of the so-called hereditary cases do not have any previous family history of retinoblastoma, and it should be emphasized that affected individuals with no such family history are in most cases the product of new germinal mutations. Retinoblastoma gene carriers acquire chiefly bilateral tumors, although sometimes only unilateral tumor. In fact, there are some individuals who develop no tumor even though a parent and a child have one or more. In such instances it seems certain that the individual carries the gene but is not affected. The precise fraction of gene carriers who do not develop tumor is unknown but is of the order of magnitude of 5%. At the other extreme some persons not only have bilateral tumors but have several primary tumors in one eye. The number of tumors acquired by a gene carrier seems to ,