Yoo Nam J, Kim S, Lee Sug H
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul 137-701, Korea.
Dig Dis Sci. 2009 May;54(5):1011-4. doi: 10.1007/s10620-008-0458-9. Epub 2008 Aug 22.
A recent study of Wilms' tumors discovered a new X chromosome gene, Wilms' tumor gene on the X chromosome (WTX), which was found to harbor small deletions and point mutations. WTX protein negatively regulates Wnt/ beta-catenin signaling, and is considered a tumor-suppressor gene. One of the questions about the WTX gene is whether the genetic alterations of the WTX gene are specific to only Wilms' tumors. To see whether somatic point mutations of WTX occur in other malignancies, we analyzed the WTX gene for the detection of mutations in 141 cancer tissues by a single-strand conformation polymorphism assay. The cancer tissues consisted of 47 gastric adenocarcinomas, 47 colorectal adenocarcinomas, and 47 hepatocellular carcinomas. Overall, we detected one WTX mutation in the colorectal carcinomas (1/47; 2.1%), but there was no WTX mutation in other cancers analyzed. The detected mutation was a missense mutation (c. 1117G > A (p.Ala373Thr)). Although the WTX mutation is common in Wilms' tumors, our data indicate that it is rare in colorectal, gastric, and hepatocellular carcinomas. The data also suggest that deregulation of Wnt/ beta-catenin signaling by WTX gene mutation may be a rare event in the pathogenesis of colorectal, gastric, and hepatocellular carcinomas.
最近一项针对肾母细胞瘤的研究发现了一个新的X染色体基因——X染色体上的肾母细胞瘤基因（WTX），该基因存在小片段缺失和点突变。WTX蛋白对Wnt/β-连环蛋白信号通路起负调控作用，被认为是一种肿瘤抑制基因。关于WTX基因的一个问题是，WTX基因的基因改变是否仅在肾母细胞瘤中具有特异性。为了探究WTX的体细胞点突变是否会出现在其他恶性肿瘤中，我们通过单链构象多态性分析，对141份癌组织中的WTX基因进行了突变检测。这些癌组织包括47例胃腺癌、47例结肠腺癌和47例肝细胞癌。总体而言，我们在结肠腺癌中检测到1例WTX突变（1/47；2.1%），但在分析的其他癌症中未检测到WTX突变。检测到的突变是一个错义突变（c.1117G>A（p.Ala373Thr））。尽管WTX突变在肾母细胞瘤中很常见，但我们的数据表明，它在结肠、胃和肝细胞癌中很少见。这些数据还表明，WTX基因突变导致的Wnt/β-连环蛋白信号通路失调在结肠、胃和肝细胞癌的发病机制中可能是一个罕见事件。
