Abstract：
Among pediatric renal tumors, rhabdoid tumor of the kidney (RTK) and clear cell sarcoma of the kidney (CCSK) are rare and associated with an unfavorable prognosis, while congenital mesoblastic nephroma (CMN) is associated with a good prognosis. Methylation of the Ras association domain-containing protein 1 isoform A (RASSF1A) promoter has been reported to correlate with a poor prognosis in patients with Wilms tumors, while its methylation status is unclear in other types of pediatric renal tumors.
DNA methylation of the RASSF1A promoter in several pediatric renal tumors was analyzed with pyrosequencing. In order to clarify the correlation between expression of RASSF1A and DNA methylation of its promoter, the RTK cell line was treated with 5-Aza-2\'-deoxycytidine (5-Aza-dC). RASSF1A was overexpressed in the RTK cell line to evaluate its functional effects.
Quantitative methylation analysis demonstrated hypermethylation in the RASSF1A promoter region in RTK and CCSK, but not CMN. The 5-Aza-dC treatment induced demethylation of the RASSF1A promoter as well as increased RASSF1A mRNA expression. The transduction of RASSF1A has an effect on the suppression of viability and proliferation of RTK cells.
DNA methylation-mediated deficiency of RASSF1A might be involved in the development and aggressiveness of some pediatric renal tumors and correlated with a poor prognosis.
DNA methylation of the RASSF1A promoter in several pediatric renal tumors was analyzed with pyrosequencing. In order to clarify the correlation between expression of RASSF1A and DNA methylation of its promoter, the RTK cell line was treated with 5-Aza-2\'-deoxycytidine (5-Aza-dC). RASSF1A was overexpressed in the RTK cell line to evaluate its functional effects.
Quantitative methylation analysis demonstrated hypermethylation in the RASSF1A promoter region in RTK and CCSK, but not CMN. The 5-Aza-dC treatment induced demethylation of the RASSF1A promoter as well as increased RASSF1A mRNA expression. The transduction of RASSF1A has an effect on the suppression of viability and proliferation of RTK cells.
DNA methylation-mediated deficiency of RASSF1A might be involved in the development and aggressiveness of some pediatric renal tumors and correlated with a poor prognosis.
摘要：
背景：在小儿肾脏肿瘤中，肾横纹肌样肿瘤（RTK）和肾透明细胞肉瘤（CCSK）罕见且预后不良。而先天性中胚层肾瘤（CMN）与良好的预后有关。据报道，含Ras关联域的蛋白1亚型A（RASSF1A）启动子的甲基化与Wilms肿瘤患者的不良预后相关。而其甲基化状态在其他类型的小儿肾脏肿瘤中尚不清楚。
方法：用焦磷酸测序分析了几种小儿肾脏肿瘤中RASSF1A启动子的DNA甲基化。为了阐明RASSF1A基因表达与启动子DNA甲基化的相关性,用5-Aza-2'-脱氧胞苷(5-Aza-dC)处理RTK细胞系。RASSF1A在RTK细胞系中过表达以评估其功能作用。
结果：定量甲基化分析显示RTK和CCSK的RASSF1A启动子区域过度甲基化，但不是CMN。5-Aza-dC处理诱导RASSF1A启动子的去甲基化以及增加的RASSF1AmRNA表达。RASSF1A的转导对抑制RTK细胞的活力和增殖具有作用。
结论：DNA甲基化介导的RASSF1A缺陷可能参与了某些儿童肾脏肿瘤的发展和侵袭性，并与预后不良有关。
方法：用焦磷酸测序分析了几种小儿肾脏肿瘤中RASSF1A启动子的DNA甲基化。为了阐明RASSF1A基因表达与启动子DNA甲基化的相关性,用5-Aza-2'-脱氧胞苷(5-Aza-dC)处理RTK细胞系。RASSF1A在RTK细胞系中过表达以评估其功能作用。
结果：定量甲基化分析显示RTK和CCSK的RASSF1A启动子区域过度甲基化，但不是CMN。5-Aza-dC处理诱导RASSF1A启动子的去甲基化以及增加的RASSF1AmRNA表达。RASSF1A的转导对抑制RTK细胞的活力和增殖具有作用。
结论：DNA甲基化介导的RASSF1A缺陷可能参与了某些儿童肾脏肿瘤的发展和侵袭性，并与预后不良有关。
