EPIGENETIC LESIONS AT THE H19 LOCUS IN WILMS-TUMOR PATIENTS
EPIGENETIC LESIONS AT THE H19 LOCUS IN WILMS-TUMOR PATIENTS
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DOI：
10.1038/ng0794-440
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发表时间：
1994-07-01
期刊：
影响因子：
30.8
通讯作者：
TYCKO, B
中科院分区：
文献类型：
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作者：
MOULTON, T;CRENSHAW, T;TYCKO, B
为了测试H19作为肿瘤抑制基因的潜在作用，我们检测了它在Wilms肿瘤（WTs）中的表达和DNA甲基化。在大多数WTs（18/25）中，H19 RNA比胎儿肾脏水平至少降低了20倍。在表达阴性的肿瘤中，10例保留11p15.5杂合性：其中9例H19 DNA双等位高甲基化，在2例非肿瘤性肾实质中也存在局部局限于H19序列的高甲基化。IGF2 mRNA在大部分WTs中均有表达，且表达模式与IGF2/H19增强子竞争一致，不存在反向偶联。这些观察结果暗示了H19在Wilms肿瘤发生中的遗传和表观遗传失活。
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.