Progress on several unresolved issues in cancer epigenetics will benefit from 
rapid and standardized methods for profiling DNA methylation genome-wide. In the 
area of epigenetic therapy, the demethylating drug decitabine 
(5-aza-2'-deoxycytidine) is increasingly used to treat acute myelogenous 
leukemia and myelodysplastic syndrome, but the mechanisms of its anticancer 
activity have remained unclear. Given the clinical efficacy of decitabine and 
the uncertainties about its mode of action, it will be useful to optimize 
methods for following DNA methylation as a biochemical response in individual 
patients. Here, we describe a single nucleotide polymorphism (SNP) chip-based 
method (MSNP) for profiling DNA methylation. Using this procedure, the extent of 
demethylation in bone marrow aspirates from patients with leukemia receiving 
decitabine can be assessed genome-wide using commercially available (Affymetrix) 
SNP chips. We validated the accuracy of MSNP by comparing the results with 
combined bisulfite restriction analysis and by sequencing cloned PCR products 
from bisulfite-converted DNA. We further validated MSNP in a Wilms' tumor/normal 
kidney comparison, comparing the results with methylation-sensitive Southern 
blotting. MSNP simultaneously detects aberrations in DNA copy number and loss of 
heterozygosity, making it a generally useful approach for combined genetic and 
epigenetic profiling in tissue samples from cancer patients.