Gunning K B, Cohn S L, Tomlinson G E, Strong L C, Huff V
Department of Experimental Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, USA.
Oncogene. 1996 Sep 19;13(6):1179-85.
WT1 RNA processing abnormalities have been suggested to play a role in the development of Wilms tumor by reports of editing at codon 280 in the rat WT1 transcript (codon 281 in humans) and aberrant splicing of exon 2 in WT1 transcripts from Wilms tumor xenograft cell lines. Both events result in a functionally changed WT1 protein and are potential mechanisms of altering normal protein function in the absence of WT1 DNA mutations. To determine whether either of these RNA processing events occurs in primary Wilms tumors, we analysed WT1 mRNA from 15 primary tumors. There was no evidence of WT1 RNA editing at codon 281, and only one primary tumor displayed aberrant splicing of exon 2. Sequence and Southern analysis of DNA from this tumor did not reveal any alteration in or around exon 2. These results suggest that neither RNA editing at codon 281 nor aberrant exon 2 splicing is a frequent mechanism of WT1 alteration during tumorigenesis.
通过大鼠WT1转录本中密码子280（人类为密码子281）的编辑报道以及来自肾母细胞瘤异种移植细胞系的WT1转录本中外显子2的异常剪接，提示WT1 RNA加工异常在肾母细胞瘤的发生中起作用。这两个事件均导致功能改变的WT1蛋白，并且是在无WT1 DNA突变情况下改变正常蛋白功能的潜在机制。为了确定这些RNA加工事件是否在原发性肾母细胞瘤中发生，我们分析了15例原发性肿瘤的WT1 mRNA。没有证据表明密码子281处存在WT1 RNA编辑，并且只有一例原发性肿瘤显示外显子2异常剪接。对该肿瘤的DNA进行序列和Southern分析未发现外显子2及其周围有任何改变。这些结果表明，密码子281处的RNA编辑和外显子2异常剪接均不是肿瘤发生过程中WT1改变的常见机制。
