GSE136986
DNA methylation profile of Korean CLL patients and normal controls
We performed genome-wide methylation profiling of CLL in an Asian cohort for the first time. Eight Korean patients without somatic immunoglobulin heavy chain gene hypermutations underwent methyl-CpG binding domain sequencing (MBD-seq), as did five control subjects. Gene Ontology, pathway analysis, and network-based prioritization of differentially methylated genes were also performed. We found more hypomethylated regions (2,062 windows) than hypermethylated regions (777 windows). Promoters contained the highest proportion of differentially methylated regions (DMRs; approximately 0.08%), while distal intergenic and intron regions contained the largest number of DMRs. Protein-coding genes were the most abundant, followed by long noncoding and short noncoding genes. The most significantly dysregulated signaling pathways included immune/cancer-related pathways and B-cell receptor signaling. Among the top 10 hub genes identified via network-based prioritization, four novel candidate genes (UBC, GRB2, CREBBP, and GAB2) had no known relevance to CLL while the other six (STAT3, PTPN6, SYK, STAT5B, XPO1, and ABL1) have previously been linked to CLL in Caucasians. As such, our analysis identified four novel candidate genes of potential significance to Asian patients with CLL. Overall design: Bone marrow buffy coats were collected from eight Korean CLL patients without IGHV mytations. CD19 positive B-cells were collected from five healthy donors using magnetic bead sorting. DNA methylation profiles of the eight patients and five controls were generated by MeDIP-Seq.