title: DNA methylation in multiple myeloma is weakly associated with gene transcription.
abstract: Previous studies have now demonstrated that both genic and global hypomethylation characterizes the multiple myeloma (MM) epigenome. Whether these methylation changes are associated with global and corresponding increases (or decreases) in transcriptional activity are poorly understood. The purpose of our current study was to correlate DNA methylation levels in MM to gene expression. We analyzed matching datasets generated by the GoldenGate methylation BeadArray and Affymetrix gene expression platforms in 193 MM samples. We subsequently utilized two independent statistical approaches to identify methylation-expression correlations. In the first approach, we used a linear correlation parameter by computing a Pearson correlation coefficient. In the second approach, we discretized samples into low and high methylation groups and then compared the gene expression differences between the groups. Only methylation of 2.1% and 25.3% of CpG sites on the methylation array correlated to gene expression by Pearson correlation or the discretization method, respectively. Among the genes with methylation-expression correlations were IGF1R, DLC1, p16, and IL17RB. In conclusion, DNA methylation may directly regulate relatively few genes and suggests that additional studies are needed to determine the effects of genome-wide methylation changes in MM.
authors.affiliation: Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, Arizona, USA.
authors.forename: Sungwon
authors.initials: S
authors.lastname: Jung
authors.forename: Seungchan
authors.initials: S
authors.lastname: Kim
authors.forename: Molly
authors.initials: M
authors.lastname: Gale
authors.forename: Irene
authors.initials: I
authors.lastname: Cherni
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.forename: John
authors.initials: J
authors.lastname: Carpten
authors.forename: Bodour
authors.initials: B
authors.lastname: Salhia
mesh_terms: D002869:Chromosome Aberrations; D019295:Computational Biology / Q000379:methods; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics*; D015203:Reproducibility of Results; D014158:Transcription, Genetic