MUTATION AND CANCER - STATISTICAL STUDY OF RETINOBLASTOMA
MUTATION AND CANCER - STATISTICAL STUDY OF RETINOBLASTOMA
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DOI：
10.1073/pnas.68.4.820
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发表时间：
1971-01-01
影响因子：
11.1
通讯作者：
KNUDSON, AG
中科院分区：
文献类型：
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作者：
KNUDSON, AG
根据对48例视网膜母细胞瘤的观察和已发表的报告，提出视网膜母细胞瘤是由两个突变事件引起的癌症的假设。在显性遗传形式中，一种突变通过生发细胞遗传，另一种突变发生在体细胞中。在非遗传形式中，这两种突变都发生在体细胞中。第二个突变平均每个遗传第一个突变的人产生三个视网膜母细胞瘤。使用泊松统计，我们可以计算出这个数字(3)可以解释偶尔没有肿瘤的基因携带者，那些只发展为单侧肿瘤的人，以及那些发展为双侧肿瘤的人，以及解释单眼多发肿瘤的情况。在基因携带者中发生肿瘤的平均数目的这个值可以用来估计每个突变的突变率。第一种方法的生发率和体细胞率，以及第二种方法（突变）的体细胞率大致相等。生发突变在某些情况下可能是由延迟突变引起的。
Based upon observations on 48 cases of retinoblastoma and published reports, the hypothesis is developed that retinoblastoma is a cancer caused by two mutational events. In the dominantly inherited form, one mutation is inherited via the germinal cells and the second occurs in somatic cells. In the nonhereditary form, both mutations occur in somatic cells.The second mutation produces an average of three retinoblastomas per individual inheriting the first mutation. Using Poisson statistics, one can calculate that this number (three) can explain the occasional gene carrier who gets no tumor, those who develop only unilateral tumors, and those who develop bilateral tumors, as well as explaining instances of multiple tumors in one eye.This value for the mean number of tumors occurring in genetic carriers may be used to estimate the mutation rate for each mutation. The germinal and somatic rates for the first, and the somatic rate for the second, mutation, are approximately equal. The germinal mutation may arise in some instances from a delayed mutation.