Different incidences of epigenetic but not genetic abnormalities between W ilms tumors in J apanese and C aucasian children

Epidemiological studies show that the incidence of Wilms tumor ( WT ) in East‐ A sian 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 β‐catenin degradation complex; however, the relationship between WTX abnormality and CTNNB1 mutation was uncertain in WT s. We examined abnormalities of the four genes in 114 Japanese with WT s to clarify the relationship between genetic and epigenetic factors and the incidence of WT s. We found that abnormalities of WTX and CTNNB1 were mutually exclusive, and that although CTNNB1 mutation was frequent in WT s with WT1 abnormality, but rare in WT s without, the incidences of WTX abnormality were similar between WT s 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 WT s, respectively. When we selected 101 sporadic WT s, 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 WT s in Japanese children. ( Cancer Sci 2012; 103: 1129–1135)