bspp : bisulfite padlock probe ; charm : comprehensive high - throughput arrays for relative methylation ; cimp : cpg island methylator phenotype ; esc : embryonic stem cell ; fda : food and drug administration ; help : hpaii tiny fragment enrichment by ligation - mediated pcr ; mca : methylated cpg island amplification ; mcam : methylated cpg island amplification microarray ; medip : methylated dna immunoprecipitation ; mira : methylated - cpg island recovery assay ; mscc : methyl - sensitive cut counting ; pcr : polymerase chain reaction ; rrbs : reduced representation bisulfite sequencing .
the authors are supported by the leukemia specialized program of research excellence grant p50 ca100632 .
 dna methylation of promoter cpg islands is strongly associated with gene silencing and is known as a frequent cause of loss of expression of tumor suppressor genes , as well as other genes involved in tumor formation . 
 dna methylation of driver genes is very likely outnumbered by the number of methylated passenger genes , though these can be useful as tumor markers . 
 much of what is known about the importance of dna methylation in cancer was gained through small- and moderate - scale analysis of gene promoters and tumor samples . a much better understanding of the role of dna methylation in cancer , either as a marker of disease or as an active driver of tumorigenesis , will likely be gained from genome - wide studies of this modification in normal and malignant cells . 
 this goal has become more attainable with the recent introduction of large - scale genome analysis methodologies and these have been modified to allow for investigation of dna methylation . 
 several research groups have been formed to coordinate efforts and apply these methodologies to decipher the methylome of healthy and diseased tissues . in this article 
 we review technological advances in genome - wide methylation profiling . 
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