Different incidences of epigenetic but not genetic abnormalities between Wilms tumors in Japanese and Caucasian children

Masayuki Haruta, Yasuhito Arai, Naoki Watanabe, Yuiko Fujiwara, Shohei Honda, Junjiro Ohshima, Fumio Kasai, Hisaya Nakadate, Hiroshi Horie, Hajime Okita, Jun Ichi Hata, Masahiro Fukuzawa, Yasuhiko Kaneko

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15 Citations (Scopus)

Abstract

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 β-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.

Original languageEnglish
Pages (from-to)1129-1135
Number of pages7
JournalCancer science
Volume103
Issue number6
DOIs
Publication statusPublished - 2012 Jun 1
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Haruta, M., Arai, Y., Watanabe, N., Fujiwara, Y., Honda, S., Ohshima, J., Kasai, F., Nakadate, H., Horie, H., Okita, H., Hata, J. I., Fukuzawa, M., & Kaneko, Y. (2012). Different incidences of epigenetic but not genetic abnormalities between Wilms tumors in Japanese and Caucasian children. Cancer science, 103(6), 1129-1135. https://doi.org/10.1111/j.1349-7006.2012.02269.x