Methylation of DNA is a modification of one of DNA four bases, cytosine, that plays an important part in regulating expression of the cellular genetic material. Accumulating evidence indicates that abnormal DNA methylation has profound effects in tumorigenesis of multiple myelomas. Understanding the regulation of gene expression by DNA methylation will open an unprecedented window into the nature of myelomas. We will employ innovative microarray profiling of DNA methylation and gene expression in this proposal to define Epigenomic Signature of Myeloma that improves our understanding of this disease and potentially set the stage for carefully designed clinical trials essential to achieve curative potential.