title: Genome-wide DNA methylation analysis reveals novel epigenetic changes in chronic lymphocytic leukemia.
abstract: We conducted a genome-wide DNA methylation analysis in CD19 (+)  B-cells from chronic lymphocytic leukemia (CLL) patients and normal control samples using reduced representation bisulfite sequencing (RRBS). The methylation status of 1.8-2.3 million CpGs in the CLL genome was determined; about 45% of these CpGs were located in more than 23,000 CpG islands (CGIs). While global CpG methylation was similar between CLL and normal B-cells, 1764 gene promoters were identified as being differentially methylated in at least one CLL sample when compared with normal B-cell samples. Nineteen percent of the differentially methylated genes were involved in transcriptional regulation. Aberrant hypermethylation was found in all HOX gene clusters and a significant number of WNT signaling pathway genes. Hypomethylation occurred more frequently in the gene body including introns, exons, and 3'-UTRs in CLL. The NFATc1 P2 promoter and first intron was found to be hypomethylated and correlated with upregulation of both NFATc1 RNA and protein expression levels in CLL suggesting that an epigenetic mechanism is involved in the constitutive activation of NFAT activity in CLL cells. This comprehensive DNA methylation analysis will further our understanding of the epigenetic contribution to cellular dysfunction in CLL.
authors.affiliation: GHSU Cancer Center; Georgia Health Sciences University; Augusta, GA, USA.
authors.forename: Lirong
authors.initials: L
authors.lastname: Pei
authors.forename: Jeong-Hyeon
authors.initials: JH
authors.lastname: Choi
authors.forename: Jimei
authors.initials: J
authors.lastname: Liu
authors.forename: Eun-Joon
authors.initials: EJ
authors.lastname: Lee
authors.forename: Brian
authors.initials: B
authors.lastname: McCarthy
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
authors.forename: Ethan
authors.initials: E
authors.lastname: Speir
authors.forename: Farrukh
authors.initials: F
authors.lastname: Awan
authors.forename: Hongseok
authors.initials: H
authors.lastname: Tae
authors.forename: Gerald
authors.initials: G
authors.lastname: Arthur
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Schnabel
authors.forename: Kristen H
authors.initials: KH
authors.lastname: Taylor
authors.forename: Xinguo
authors.initials: X
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
authors.forename: Han-Fei
authors.initials: HF
authors.lastname: Ding
authors.forename: David H
authors.initials: DH
authors.lastname: Munn
authors.forename: Charles
authors.initials: C
authors.lastname: Caldwell
authors.forename: Huidong
authors.initials: H
authors.lastname: Shi
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005801:Genes, Homeobox; D015894:Genome, Human; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D050778:NFATC Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D050778:NFATC Transcription Factors; D051153:Wnt Proteins