[Methylation status of LINE-1 sequences in patients with MDS or secondary AML].

D Römermann, B Hasemeier, K Metzig, B Schlegelberger, F Länger, H Kreipe, U Lehmann
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Abstract

Objectives: This study analyzes changes in the degree of global methylationlevel in myelodysplastic syndrome during progression of the disease.

Methods: 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.

Results: 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.

Conclusions: 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.

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[LINE-1序列在MDS或继发性AML患者中的甲基化状态]。
目的:本研究分析骨髓增生异常综合征在疾病进展过程中全球甲基化水平的变化。方法:分析127例经组织学证实的MDS患者和26例反应性对照者的甲基化状态。我们采用焦磷酸测序,发光甲基化测定(LUMA)和实时pcr为基础的定量分析。结果:我们使用焦磷酸测序检测到LINE-1序列甲基化水平的增加,并且在MDS的进展过程中使用LUMA检测到HpaII识别位点甲基化水平的增加。甲基化敏感定量PCR无统计学差异,仅呈趋势。结论:LINE-1和甲基化敏感的DNA切割可以作为全球DNA甲基化的替代标记。MDS的全基因组高甲基化是该疾病的一个明显特征。它将MDS与其他肿瘤区分开来,并可能解释azadeoxycytidine等低甲基化诱导试剂在MDS治疗中的成功。
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