Römermann D, Hasemeier B, Metzig K, Schlegelberger B, Länger F, Kreipe H, Lehmann U
Institut für Pathologie, Medizinische Hochschule Hannover.
Verh Dtsch Ges Pathol. 2007;91:338-42.
This study analyzes changes in the degree of global methylationlevel in myelodysplastic syndrome during progression of the disease.
Methylation status was analyzed in 127 patients with histologically confirmed MDS and 26 reactive controls. We employed Pyrosequencing, Luminometric Methylation Assay (LUMA) and a realtime PCR-based quantitative assay.
We detected an increase of methylation level of LINE-1 sequences using pyrosequencing and an increase of methylation in the HpaII recognition site employing LUMA during the progression of MDS. Methylation sensitive quantitative PCR showed no statistically significant differences, only a trend.
LINE-1 and methylation sensitive cleavage of DNA can act as a surrogatmarker for global DNA methylation. The genome wide hypermethylation of MDS is a distinct feature of this disease. It discriminates MDS from other neoplasia and may explains the success of hypomethylation inducing reagents like azadeoxycytidine in MDS therapy.
本研究分析骨髓增生异常综合征疾病进展过程中整体甲基化水平程度的变化。
对127例经组织学确诊的骨髓增生异常综合征患者和26例反应性对照者的甲基化状态进行分析。我们采用了焦磷酸测序、荧光定量甲基化分析（LUMA）和基于实时聚合酶链反应的定量分析方法。
在骨髓增生异常综合征进展过程中，我们通过焦磷酸测序检测到LINE-1序列甲基化水平升高，采用LUMA检测到HpaII识别位点甲基化增加。甲基化敏感定量聚合酶链反应未显示出统计学上的显著差异，只有一种趋势。
LINE-1和对甲基化敏感的DNA切割可作为整体DNA甲基化的替代标志物。骨髓增生异常综合征的全基因组高甲基化是该疾病的一个显著特征。它将骨髓增生异常综合征与其他肿瘤区分开来，并可能解释了诸如阿扎胞苷等去甲基化诱导试剂在骨髓增生异常综合征治疗中取得成功的原因。
