Subject(s)
DNA Methylation , Myelodysplastic Syndromes/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Cyclin-Dependent Kinase Inhibitor p15/genetics , Female , Humans , Male , Middle AgedABSTRACT
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.