Mutation and cancer: a model for Wilms' tumor of the kidney.
Mutation and cancer: a model for Wilms' tumor of the kidney.
复制标题
突变和癌症：肾维尔姆斯氏肿瘤模型。
DOI：
10.1093/jnci/48.2.313
复制
发表时间：
1972
期刊：
影响因子：
--
通讯作者：
L. Strong
中科院分区：
文献类型：
--
作者：
A. Knudson;A. Knudson;L. Strong
对Wilms肿瘤病例的统计分析支持先前报道的视网膜母细胞瘤的双突变模型。对家族性、双侧、单侧和未选择病例的数据进行比较，发现家族性和双侧病例的平均诊断年龄较早，其分布提示为单一事件过程，而单侧和未选择病例则不然。家族性病例的双侧性发生率高于未选择病例，其模式与常染色体显性遗传一致。这些发现表明，Wilms的肿瘤可能归因于一个双突变模型；在所有情况下都需要2个突变，但是，在大约38%的情况下，一个突变发生在亲本的生发系中并被遗传。获得这种生发突变的人平均每秒钟发生突变，从而导致肿瘤。大约37%的基因携带者不发展为肿瘤，15%发展为双侧肿瘤。约62%的Wilms肿瘤是非遗传性的，这两种突变都发生在体细胞中。Wilms肿瘤与无虹膜、半肥厚和泌尿生殖系统异常的关系符合该模型。家族模式被认为与延迟突变相似；新的生发突变可能归因于一种垂直传播的肿瘤病毒，类似于引起鸡胚胎性肾肉瘤的病毒。
Statistical analysis of cases of Wilms' tumor supports a 2-mutation model previously reported for retinoblastoma. Comparison of data for familial, bilateral, unilateral, and unselected cases reveals that familial and bilateral cases have an early average age of diagnosis, with a distribution suggestive of a single-event process, while unilateral and unselected cases do not. Familial cases have an incidence of bilaterality higher than that of unselected cases and a pattern consistent with autosomal dominant inheritance. These findings suggest that Wilms' tumor may be attributed to a 2-mutational model;i.e., 2 mutations are required in all cases, but, in approximately 38%, one mutation has occurred in the germinal line of a parent and is inherited. Persons acquiring this germinal mutant develop an average of one second mutation each, which gives rise to tumor. Approximately 37% of gene carriers do not develop tumor, and 15% develop bilateral tumors. About 62% of cases of Wilms' tumor are non-hereditary, both of the mutations occurring in somatic cells. The association of Wilms' tumor with aniridia, hemihypertrophy, and genitourinary anomalies is fitted to the model. The familial pattern is noted to be similar to that of a delayed mutation; new germinal mutations may be attributable to a vertically transmitted tumor virus resembling the virus causing embryonal renal sarcoma in chickens.