Different incidences of epigenetic but not genetic abnormalities between Wilms tumors in Japanese and Caucasian children
Different incidences of epigenetic but not genetic abnormalities between Wilms tumors in Japanese and Caucasian children
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DOI：
10.1111/j.1349-7006.2012.02269.x
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发表时间：
2012-06-01
期刊：
影响因子：
5.7
通讯作者：
Kaneko, Yasuhiko
中科院分区：
文献类型：
--
作者：
Haruta, Masayuki;Arai, Yasuhito;Kaneko, Yasuhiko
流行病学研究表明，东亚儿童的肾母细胞瘤（WT）发病率是白人儿童的一半。据报道，WT 1、CTNNB 1、WTX和IGF 2的缺失与白种人的肾母细胞瘤发生有关，尽管没有研究同时评估这四个基因。WTX形成β-连环蛋白降解复合物;然而，WTX异常与CTNNB 1突变之间的关系在WT中尚不确定。我们检查了114例日本WT患者的四个基因的异常，以阐明遗传和表观遗传因素与WT发病率之间的关系。我们发现WTX和CTNNB 1的异常是相互排斥的，虽然CTNNB 1突变在WT 1异常的WT中很常见，而在WT 1不异常的WT中很少见，但WTX异常的发生率在WT 1异常和无WT 1异常的WT中相似。这些结果与高加索人群中报告的结果一致，并表明WTX异常的多种作用。WT 1、WTX和CTNNB 1的缺失和IGF 2印迹（LOI）的缺失分别占31.6%、22.8%、26.3%和21.1%。当我们选择101例散发性WT时，两个人群中WT 1、CTNNB 1或WTX异常的发生率基本相当，而日本人中IGF 2 LOI的发生率低于高加索人中IGF 2 LOI的发生率（P = 0.04）。这是第一次对这四个基因进行全面研究，结果支持了IGF 2 LOI发生率较低导致日本儿童WT发生率较低的假设。（Cancer Sci 2012; 103：11291135）
Epidemiological studies show that the incidence of Wilms tumor (WT) in East-Asian children is half of that in Caucasian children. Abnormalities of WT1, CTNNB1, WTX, and IGF2 were reported to be involved in Wilms tumorigenesis in Caucasians, although none of the studies simultaneously evaluated the four genes. WTX forms the beta-catenin degradation complex; however, the relationship between WTX abnormality and CTNNB1 mutation was uncertain in WTs. We examined abnormalities of the four genes in 114 Japanese with WTs to clarify the relationship between genetic and epigenetic factors and the incidence of WTs. We found that abnormalities of WTX and CTNNB1 were mutually exclusive, and that although CTNNB1 mutation was frequent in WTs with WT1 abnormality, but rare in WTs without, the incidences of WTX abnormality were similar between WTs with or without WT1 abnormality. These findings were consistent with those reported in Caucasian populations, and indicate multiple roles of WTX abnormality. Abnormalities of WT1, WTX and CTNNB1, and loss of IGF2 imprinting (LOI) were detected in 31.6%, 22.8%, 26.3%, and 21.1% of the 114 WTs, respectively. When we selected 101 sporadic WTs, the incidences of WT1, CTNNB1, or WTX abnormality were generally comparable between the two populations, whereas the incidence of IGF2 LOI was lower in Japanese than that of IGF2 LOI reported in Caucasians (P = 0.04). This is the first comprehensive study of the four genes, and the results supported the hypothesis that the lower incidence of IGF2 LOI contributes to the lower incidence of WTs in Japanese children. (Cancer Sci 2012; 103: 11291135)