Yeger H, Cullinane C, Flenniken A, Chilton-MacNeil S, Campbell C, Huang A, Bonetta L, Coppes M J, Thorner P, Williams B R
Department of Pathology, Hospital For Sick Children, Toronto, Ontario, Canada.
Cell Growth Differ. 1992 Dec;3(12):855-64.
The cloning and molecular characterization of two putative tumor genes, WT1 and WIT1, from the chromosome 11p13 region has provided a means of evaluating their role in the generation of Wilms' tumor heterogeneity. A series of 29 tumors were analyzed for WT1 and WIT1 expression by Northern blot or RNase protection analyses, and results were compared with tumor histopathology. Tumors were scored for the percentage of mesenchymal and epithelial derived tissue components. Homotypic tumors comprised blastema, tubular epithelium, and a fibroblast-like mesenchyme. In addition to these tissue components, the group of tumors designated as heterotypic also contained ectopic cell phenotypes such as muscle and squamous epithelium. The analyses suggest that heterotypic differentiation patterns occur when WT1 and WIT1 expression is low relative to normal fetal kidney. In situ hybridization using antisense RNA probes showed that WT1 and WIT1 were concordantly expressed in normal fetal kidney and in the blastema of tumors. The ratio of WT1:WIT1 expression remained relatively constant in homotypic tumors but deviated significantly in heterotypic tumors. These results suggest that expression patterns of the WT1 and WIT1 genes can be closely correlated to Wilms' tumor histopathology.
从11号染色体p13区域克隆并对两个假定的肿瘤基因WT1和WIT1进行分子特征分析，为评估它们在肾母细胞瘤异质性产生中的作用提供了一种方法。通过Northern印迹或核糖核酸酶保护分析对一系列29个肿瘤进行WT1和WIT1表达分析，并将结果与肿瘤组织病理学进行比较。对肿瘤的间充质和上皮来源组织成分的百分比进行评分。同型肿瘤包括胚基、管状上皮和成纤维细胞样间充质。除了这些组织成分外，被指定为异型的肿瘤组还包含异位细胞表型，如肌肉和鳞状上皮。分析表明，当WT1和WIT1表达相对于正常胎儿肾脏较低时，会出现异型分化模式。使用反义RNA探针的原位杂交显示，WT1和WIT1在正常胎儿肾脏和肿瘤胚基中一致表达。WT1:WIT1表达比率在同型肿瘤中保持相对恒定，但在异型肿瘤中显著偏离。这些结果表明，WT1和WIT1基因的表达模式可能与肾母细胞瘤的组织病理学密切相关。
