Huff V, Miwa H, Haber D A, Call K M, Housman D, Strong L C, Saunders G F
Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Am J Hum Genet. 1991 May;48(5):997-1003.
The inactivation of two alleles at a locus on the short arm of chromosome 11 (band 11p13) has been suggested to be critical steps in the development of Wilms tumor (WT), a childhood kidney tumor. Two similar candidate WT cDNA clones (WT33 and LK15) have recently been identified on the basis of both their expression in fetal kidney and their location within the smallest region of overlap of somatic 11p13 deletions in some tumors. These homozygous deletions, however, are large and potentially affect more than one gene. Using a cDNA probe to the candidate gene, we have analyzed DNA from both normal and tumor tissue from WT patients, in an effort to detect rearrangements at this locus. We report here a patient with bilateral WT who is heterozygous for a small (less than 11 kb) germinal deletion within this candidate gene. DNA from both tumors is homozygous for this intragenic deletion allele, which, by RNA-PRC sequence analysis, is predicted to encode a protein truncated by 180 amino acids. These data support the identification of this locus as an 11p13 WT gene (WT1) and provide direct molecular data supporting the two-hit mutational model for WT.
11号染色体短臂（11p13带）上一个位点的两个等位基因失活被认为是儿童肾肿瘤——肾母细胞瘤（WT）发生发展中的关键步骤。最近，基于两个相似的候选WT cDNA克隆（WT33和LK15）在胎儿肾脏中的表达以及它们在某些肿瘤中11p13体细胞缺失最小重叠区域内的位置，这两个克隆被鉴定出来。然而，这些纯合缺失很大，可能会影响不止一个基因。我们使用候选基因的cDNA探针，分析了WT患者正常组织和肿瘤组织的DNA，以检测该位点的重排情况。我们在此报告一名双侧WT患者，其在该候选基因内存在一个小的（小于11 kb）生殖系缺失，为杂合状态。两个肿瘤的DNA对于该基因内缺失等位基因为纯合状态，通过RNA - PCR序列分析预测，该等位基因编码的蛋白质截短了180个氨基酸。这些数据支持将该位点鉴定为11p13 WT基因（WT1），并提供了直接的分子数据支持WT的双打击突变模型。
