There is disclosed a process for detection of
DNA methylation at CpG sites using
nucleic acid arrays and preferably microarrays. Specifically, there is disclosed a process for directly generating a
reference sample from the sample to be tested and detecting
methylation at large numbers of CpG island sites simultaneously. More specifically, the inventive process comprises dividing
a DNA sample into two samples (a first sample and a second sample), amplifying the first
DNA sample by a
nucleic acid amplification process such that any methylcytosine residues are amplified as unmethylated
cytosine residues, treating the amplified first sample and the (unamplified) second sample with
bisulfite to convert unmethylated
cytosine residues in both samples to deoxyuracil residues, labeling the
bisulfite-converted second sample with a second fluorescent marker and the
bisulfite-converted first sample with a first fluorescent marker, wherein the first and second fluorescent markers have non-overlapping fluorescent excitation and emission spectra; and hybridizing the first sample and the second sample onto a
microarray device having a plurality of
oligonucleotide capture probes designed to hybridize to CpG island sites of the
DNA sample as converted and non-converted by bisulfite.