Moulton T, Crenshaw T, Hao Y, Moosikasuwan J, Lin N, Dembitzer F, Hensle T, Weiss L, McMorrow L, Loew T, Kraus W, Gerald W, Tycko B
Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Nat Genet. 1994 Jul;7(3):440-7. doi: 10.1038/ng0794-440.
To test the potential role of H19 as a tumour suppressor gene we have examined its expression and DNA methylation in Wilms' tumours (WTs). In most WTs (18/25), H19 RNA was reduced at least 20-fold from fetal kidney levels. Of the expression-negative tumours ten retained 11p15.5 heterozygosity: in nine of these, H19 DNA was biallelically hypermethylated and in two cases hypermethylation locally restricted to H19 sequences was also present in the non-neoplastic kidney parenchyma. IGF2 mRNA was expressed in most but not all WTs and expression patterns were consistent with IGF2/H19 enhancer competition without obligate inverse coupling. These observations implicate genetic and epigenetic inactivation of H19 in Wilms' tumorigenesis.
为了测试H19作为肿瘤抑制基因的潜在作用，我们检测了其在肾母细胞瘤（WTs）中的表达及DNA甲基化情况。在大多数肾母细胞瘤（18/25）中，H19 RNA水平较胎儿肾脏水平降低了至少20倍。在表达阴性的肿瘤中，有10个保留了11p15.5杂合性：其中9个H19 DNA发生双等位基因高甲基化，在2个病例中，非肿瘤性肾实质中也存在局部限于H19序列的高甲基化。大多数但并非所有肾母细胞瘤中均表达IGF2 mRNA，其表达模式与IGF2/H19增强子竞争一致，但并非必然呈反向偶联。这些观察结果表明H19的基因和表观遗传失活与肾母细胞瘤的发生有关。
