Pelletier J, Bruening W, Li F P, Haber D A, Glaser T, Housman D E
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Nature. 1991 Oct 3;353(6343):431-4. doi: 10.1038/353431a0.
Wilms' tumour (WT), aniridia, genitourinary abnormalities and mental retardation form a symptom group (WAGR syndrome) associated with hemizygous deletions of DNA in chromosome band 11p13 (refs 1,2). However, it has not been clear whether hemizygosity at a single locus contributes to more than one phenotype. The tumour suppressor gene for Wilms' tumour, WT1, has been characterized: it is expressed at high levels in the glomeruli of the kidney, as well as the gonadal ridge of the developing gonad, the Sertoli cells of the testis and the epithelial and granulosa cells of the ovary, suggesting a developmental role in the genital system in addition to the kidney. We now report constitutional mutations within the WT1 genes of two individuals with a combination of WT and genital abnormalities as evidence of a role for a recessive oncogene in mammalian development.
肾母细胞瘤（WT）、无虹膜、泌尿生殖系统异常和智力发育迟缓构成了一个症状群（WAGR综合征），与染色体11p13带的DNA半合子缺失相关（参考文献1,2）。然而，单个基因座的半合子状态是否导致多种表型尚不清楚。肾母细胞瘤的肿瘤抑制基因WT1已得到鉴定：它在肾小体中高水平表达，也在发育中的性腺的生殖嵴、睾丸的支持细胞以及卵巢的上皮细胞和颗粒细胞中表达，这表明它除了在肾脏中发挥作用外，在生殖系统发育中也有作用。我们现在报告了两名患有肾母细胞瘤和生殖系统异常的个体的WT1基因中的组成性突变，作为隐性癌基因在哺乳动物发育中起作用的证据。
