Methylation of the RASSF1A promoter is predictive of poor outcome among patients with Wilms tumor

Junjiro Ohshima, Masayuki Haruta, Yuiko Fujiwara, Naoki Watanabe, Yasuhito Arai, Tadashi Ariga, Hajime Okita, Tsugumichi Koshinaga, Takaharu Oue, Shiro Hinotsu, Hisaya Nakadate, Hiroshi Horie, Masahiro Fukuzawa, Yasuhiko Kaneko

研究成果: Article査読

15 被引用数 (Scopus)


Background: Wilms tumor (WT) has a survival rate of 90% following multimodality therapy. Nevertheless, there are some groups of patients with event-free survival rates less than 75%. In addition to clinical prognostic factors, loss of heterozygosity at 1p and/or 16q has been used to determine treatment intensity. However, the incidence of this abnormality is low, and new biomarkers are still needed. Procedure: We analyzed methylation status of three tumor suppressor genes; Ras-association domain family 1 protein, isoform A (RASSF1A), DCR2, and CASP8, in 84 WTs using conventional methylation-specific PCR (cMSP), and the results were correlated with outcome. Furthermore, we analyzed the methylation status of RASSF1A by quantitative MSP (qMSP) in 171 WTs, and evaluated clinical and genetic differences between the methylated and unmethylated tumors. Results: RASSF1A was the most frequently methylated gene identified by cMSP, and associated with a poor outcome. Patients with a RASSF1A-methylated tumor had shorter overall and event-free survival periods (P=0.043 and 0.018, respectively), when a cut-off value of 7% by qMSP was used. The methylation was more frequent in tumors of older children than younger children (P<0.001), and in advanced-stage tumors than early stage tumors (P=0.001). However, multivariate analysis could not confirm the prognostic significance of RASSF1A methylation, possibly because of a small number of advanced stage tumors examined. RASSF1A methylation was correlated with LOH at 1p and/or 16q (P=0.017), but not with WT1 abnormality, suggesting the methylation and LOH to involve the same tumorigenic pathway. Conclusions: The methylation status of RASSF1A might be a novel biomarker to predict outcome of WT patients.

ジャーナルPediatric Blood and Cancer
出版ステータスPublished - 2012 9

ASJC Scopus subject areas

  • 小児科学、周産期医学および子どもの健康
  • 血液学
  • 腫瘍学


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