Gessler M, König A, Moore J, Qualman S, Arden K, Cavenee W, Bruns G
Institut für Humangenetik, Philipps-Universität Marburg, Germany.
Genes Chromosomes Cancer. 1993 Jul;7(3):131-6. doi: 10.1002/gcc.2870070304.
Wilms' tumor is a childhood nephroblastoma that is postulated to arise through the inactivation of a tumor suppressor gene by a two-hit mechanism. A candidate 11p13 Wilms' tumor gene, WT1, has been cloned and shown to encode a zinc finger protein. Patients with the WAGR syndrome (Wilm's tumor, aniridia, genitourinary abnormalities, and mental retardation) have a high risk of developing Wilms' tumor and they carry constitutional deletions of one chromosome 11 allele encompassing the WT1 gene. Analysis of the remaining WT1 allele in a Wilms' tumor from a WAGR patient revealed the deletion of a single nucleotide in exon 7. This mutation likely played a key role in tumor formation, as it prevents translation of the DNA-binding zinc finger domain that is essential for the function of the WT1 polypeptide as a transcriptional regulator.
肾母细胞瘤是一种儿童期肾母细胞瘤，据推测是通过双打击机制使肿瘤抑制基因失活而产生的。一个候选的11p13肾母细胞瘤基因WT1已被克隆，并显示编码一种锌指蛋白。患有WAGR综合征（肾母细胞瘤、无虹膜、泌尿生殖系统异常和智力迟钝）的患者患肾母细胞瘤的风险很高，他们携带包含WT1基因的一条11号染色体等位基因的先天性缺失。对一名WAGR患者的肾母细胞瘤中剩余的WT1等位基因进行分析，发现外显子7中有一个单核苷酸缺失。这种突变可能在肿瘤形成中起关键作用，因为它阻止了对WT1多肽作为转录调节因子功能至关重要的DNA结合锌指结构域的翻译。
