Huang A, Campbell C E, Bonetta L, McAndrews-Hill M S, Chilton-MacNeill S, Coppes M J, Law D J, Feinberg A P, Yeger H, Williams B R
Department of Genetics, Hospital for Sick Children, Toronto, Ontario, Canada.
Science. 1990 Nov 16;250(4983):991-4. doi: 10.1126/science.2173145.
The Wilms tumor locus on chromosome 11p13 has been mapped to a region defined by overlapping, tumor-specific deletions. Complementary DNA clones representing transcripts of 2.5 (WIT-1) and 3.5 kb (WIT-2) mapping to this region were isolated from a kidney complementary DNA library. Expression of WIT-1 and WIT-2 was restricted to kidney and spleen. RNase protection revealed divergent transcription of WIT-1 and WIT-2, originating from a DNA region of less than 600 bp. Both transcripts were present at high concentrations in fetal kidney and at much reduced amounts in 5-year-old and adult kidneys. Eleven of 12 Wilms tumors classified as histopathologically heterogeneous exhibited absent or reduced expression of WIT-2, whereas only 4 of 14 histopathologically homogeneous tumors showed reduced expression. These data demonstrate a molecular basis for the pathogenetic heterogeneity in Wilms tumorigenesis.
11号染色体p13区域的肾母细胞瘤位点已被定位到一个由重叠的肿瘤特异性缺失所界定的区域。从肾脏互补DNA文库中分离出了代表定位于该区域的2.5 kb（WIT-1）和3.5 kb（WIT-2）转录本的互补DNA克隆。WIT-1和WIT-2的表达仅限于肾脏和脾脏。核糖核酸酶保护实验显示WIT-1和WIT-2的转录方向相反，起源于一个小于600 bp的DNA区域。两种转录本在胎儿肾脏中浓度很高，而在5岁及成人肾脏中的含量则大幅降低。在12个组织病理学上异质性的肾母细胞瘤中，有11个表现出WIT-2表达缺失或降低，而在14个组织病理学上同质性的肿瘤中，只有4个显示表达降低。这些数据证明了肾母细胞瘤发生过程中致病异质性的分子基础。
