D Römermann, B Hasemeier, K Metzig, B Schlegelberger, F Länger, H Kreipe, U Lehmann
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[Methylation status of LINE-1 sequences in patients with MDS or secondary AML].
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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