@article{c74c6a3631d44dae99e5e33d509db16c,
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, 1,764 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.",
keywords = "Chronic lymphocytic leukemia, DNA methylation, NFATc1, Next-generation sequencing, Reduced representation bisulfite sequencing",
author = "Lirong Pei and Choi, {Jeong Hyeon} and Jimei Liu and Lee, {Eun Joon} and Brian McCarthy and Wilson, {James M.} and Ethan Speir and Farrukh Awan and Hongseok Tae and Gerald Arthur and Schnabel, {Jennifer L.} and Taylor, {Kristen H.} and Xinguo Wang and Dong Xu and Ding, {Han Fei} and Munn, {David H.} and Caldwell, {Charles W.} and Huidong Shi",
note = "Funding Information: Finally the methylation of each CpG site was defined as the frac-We thank Drs Nicholas Chiorazzi, Kanti R. Rai and Steven L. tion of methylated reads to that of methylated and unmethylated Allen for providing the CLL samples. We also thank Dr Judith reads combined. CpGs with <5 reads were filtered out of further Giri and Ms. Sameera Qureshi of GHSU tumor bank for help-analyses. The correlation between genome-wide CpG methyla-ing collect the CLL samples. We are grateful to Dr Chiorazzi for tion across two samples was calculated using the Pearson{\textquoteright}s prod-sharing the unpublished microarray data with us. This work was uct-moment coefficient using an R script. The raw and analyzed supported in part by the National Institute of Health (Grants sequencing data from this study has been submitted to NCBI CA134304 and DA025779 to H.S.). H.S. is a Georgia Cancer Gene Expression Omnibus (ncbi.nlm.nih.gov/geo/) under acces-Coalition Distinguished Cancer Scientist. J.C. and H.T. were sion number GSE32698. supported by a National Research Foundation of Korea Grant Detection of DMRs. We used 200 bp non-overlapping win-funded by the Korean Government (NRF-2009-352-D00275).",
year = "2012",
month = jun,
doi = "10.4161/epi.20237",
language = "English (US)",
volume = "7",
pages = "567--578",
journal = "Epigenetics",
issn = "1559-2294",
publisher = "Landes Bioscience",
number = "6",
}