Genome-Wide Profiling of CpG Methylation Identifies Novel Targets of Aberrant Hypermethylation in Myeloid Leukemia

摘要: The methylation of CpG islands is associated with transcriptional repression and, in cancer, leads to the abnormal silencing tumor suppressor genes. Because aberrant hypermethylation may be used as a marker for disease, sensitive method global detection DNA events particular importance. We describe novel and robust technique, called methyl-CpG immunoprecipitation, which allows unbiased genome-wide profiling limited samples. approach based on recombinant, antibody-like protein that efficiently binds native CpG-methylated DNA. In combination island microarrays, technique was identify >100 genes aberrantly methylated three myeloid leukemia cell lines. Interestingly, within all targets, involved regulation were significantly overrepresented. More than half identified absent microarray expression studies either or normal monocytes, indicating cancer largely independent status affected gene. Most individually tested also hypermethylated primary blast cells from acute patients, suggesting our can potential disease markers. prove useful comparative analysis not only malignancies.