Wilms tumor genetics:: Mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors
Wilms tumor genetics:: Mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors
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DOI：
10.1002/gcc.20553
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发表时间：
2008-06-01
影响因子：
3.7
通讯作者：
Huff, Vicki
中科院分区：
文献类型：
--
作者：
Ruteshouser, E. Cristy;Robinson, Stephen M.;Huff, Vicki
肾母细胞瘤是遗传异质性的，直到最近只有一个肾母细胞瘤基因是已知的，WT 1在11 p13。然而，WT 1仅在20%的Wilms肿瘤中发生改变。最近，一个新的基因，WTX在Xq11.1，被报道在肾母细胞瘤突变。WTX和WT 1突变的肿瘤之间没有重叠，这表明WT 1和WTX突变可以解释大约一半的Wilms肿瘤的遗传基础。为了评估WTX突变的频率及其与WT 1突变的关系，在一个更大的（n = 125）组Wilms肿瘤中，已经彻底评估了WT 1突变，我们进行了一个完整的WTX突变分析，包括整个编码区的测序和定量PCR，以确定WTX基因的缺失。23例（18.4%）肿瘤共携带24个WTX突变，WTX突变频率低于先前观察到的频率。令人惊讶的是，我们在WT 1和CTNNB 1中任一个或两个突变的肿瘤（20.0%）和WT 1或CTNNB 1中没有突变的肿瘤（17.5%）中观察到相等的WTX突变频率。据报道，WTX在WNT/β-连环蛋白信号通路中发挥作用，有趣的是，WTX缺失/截短突变在携带编码β-连环蛋白的CTNNB 1外显子3突变的肿瘤中似乎很少见。我们的研究结果表明，WT 1和WTX突变的发生频率相似，它们在Wilms肿瘤中部分重叠，并且WT 1，WTX和CTNNB 1的突变是大约三分之一Wilms肿瘤的遗传基础。(C)2008 Wiley-Liss，Inc.
Wilms tumor is genetically heterogeneous, and until recently only one Wilms tumor gene was known, WT1 at 11p13. However, WT1 is altered in only similar to 20% of Wilms tumors. Recently a novel gene, WTX at Xq11.1, was reported to be mutated in Wilms tumors. No overlap between tumors with mutations in WTX and WT1 was noted, suggesting that WT1 and WTX mutations could account for the genetic basis of roughly half of Wilms tumors. To assess the frequency of WTX mutations and their relationship to WT1 mutations in a larger (n = 125) panel of Wilms tumors which had been thoroughly assessed for mutations in WT1, we conducted a complete mutational analysis of WTX that included sequencing of the entire coding region and quantitative PCR to identify deletions of the WTX gene. Twenty-three (18.4%) tumors carried a total of 24 WTX mutations, a lower WTX mutation frequency than that previously observed. Surprisingly, we observed an equivalent frequency of WTX mutations in tumors with mutations in either or both WT1 and CTNNB1 (20.0%) and tumors with no mutation in either WT1 or CTNNB1 (17.5%). WTX has been reported to play a role in the WNT/beta-catenin signaling pathway, and, interestingly, WTX deletion/truncation mutations appeared to be rare in tumors carrying exon 3 mutations of CTNNB1, encoding beta-catenin. Our findings indicate that WT1 and WTX mutations occur with similar frequency, that they partially overlap in Wilms tumors, and that mutations in WT1, WTX, and CTNNB1 underlie the genetic basis of about one-third of Wilms tumors. (C) 2008 Wiley-Liss, Inc.