Promoter hypermethylation of p15INK4B, HIC1, CDH1, and ER is frequent in myelodysplastic syndrome and predicts poor prognosis in early-stage patients
Promoter hypermethylation of p15INK4B, HIC1, CDH1, and ER is frequent in myelodysplastic syndrome and predicts poor prognosis in early-stage patients
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DOI：
10.1111/j.1600-0609.2005.00559.x
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发表时间：
2006-01-01
影响因子：
3.1
通讯作者：
Hokland, P
中科院分区：
文献类型：
--
作者：
Aggerholm, A;Holm, MS;Hokland, P
骨髓增生异常综合征（MDS）向急性髓系白血病（AML）转化的倾向表明这些恶性肿瘤存在共同的致病因素。在此，对37例不同阶段MDS患者细胞中与AML发生相关的4个基因的启动子CpG岛高甲基化情况进行了检测。通过对亚硫酸氢盐处理后的DNA进行聚合酶链反应扩增，然后进行变性梯度凝胶电泳来检测异常甲基化。发现p15(INK4B)的甲基化率最高（51%），其次是HIC1（32%）、CDH1（27%）和ER（19%）。与早期MDS相比，晚期MDS中≥3个基因同时高甲基化更为频繁（P = 1个基因是一个独立的不良预后因素（P < 0.05）。这些数据表明p15(INK4B)、HIC1、CDH1和ER的高甲基化对MDS的发生和预后有影响。
（原文中“P = 1 genes”表述可能有误，可能影响对内容的准确理解）
The propensity of myelodysplastic syndrome (MDS) to transform into acute myeloid leukemia (AML) suggests the existence of common pathogenic components for these malignancies. Here, four genes implicated in the development of AML were examined for promoter CpG island hypermethylation in cells from 37 patients with different stages of MDS. Aberrant methylation was detected by polymerase chain reaction amplification of bisulfite-treated DNA followed by denaturing gradient gel electrophoresis. The highest rate of methylation was found for p15(INK4B) (51%), followed by HIC1 (32%), CDH1 (27%), and ER (19%). Concurrent hypermethylation of >= 3 genes was more frequent in advanced compared with early-stage MDS (P = 1 genes was an independent negative prognostic factor (P < 0.05). These data suggest that hypermethylation of p15(INK4B), HIC1, CDH1, and ER contribute to the development and outcome of MDS.