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Expression and methylation array analysis of CD19+ B-cells from Chronic lymhocytic leukemia (CLL) patients and age matched healthy donor samples [Methylation]

ABSTRACT: Whole genome sequencing revealed CLL as a disease of the genome and epigenome defined by somatic mutations and aberrant DNA-methylation. To uncover the impact of aberrant methylation on transcription, gene expression and methylation array profiling was performed in CLL and B-cells. DNA from 13 CLL patients and 6 healthy donor samples was analyzed using MCIp-array. Custom made agilent promoter-arrays were used for analysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE67641 | GEO | 2017/01/23

SECONDARY ACCESSION(S): PRJNA280570

REPOSITORIES: GEO

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Expression and methylation array analysis of CD19+ B-cells from Chronic lymhocytic leukemia (CLL) patients and age matched healthy donor samples [Expression]

Project description:Whole genome sequencing revealed CLL as a disease of the genome and epigenome defined by somatic mutations and aberrant DNA-methylation. To uncover the impact of aberrant methylation on transcription, gene expression and methylation array profiling was performed in CLL and B-cells. RNA from 13 CLL patients and 6 healthy donor samples was analyzed on expression arrays.

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Expression and methylation array analysis of CD19+ B-cells from Chronic lymhocytic leukemia (CLL) patients and age matched healthy donor samples

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Methylation in breast cancer vs. normal tissue

2012-09-14 | GSE35263 | GEO

Expression and methylation array analysis of CD19+ B-cells from Chronic lymhocytic leukemia (CLL) patients and age matched healthy donor samples

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-01-23 | GSE67642 | GEO

CLL intraclonal fractions exhibit established and recently-acquired patterns of DNA methylation [ME]

Project description:Intraclonal subpopulations of circulating chronic lymphocytic leukemia (CLL) cells with different proliferative histories and reciprocal surface expression of CXCR4 and CD5 have been observed in the peripheral blood of CLL patients and named proliferative (PF), intermediate (IF) and resting (RF) cellular fractions. Here we found that these intraclonal circulating fractions share persistent DNA methylation signatures largely associated with the mutation status of the immunoglobulin heavy chain locus (IGHV) and their origins from distinct stages of differentiation of antigen-experienced B-cells. Increased leukemic birth rate (BR), however, showed a very limited impact on DNA methylation of circulating CLL fractions independent of IGHV mutation status. Additionally, DNA methylation heterogeneity increased as leukemic cells advanced from PF to RF in the peripheral blood. This frequently co-occurred with heterochromatin hypomethylation and hypermethylation of Polycomb-repressed regions in the PF, suggesting accumulation of longevity-associated epigenetic features in recently born cells.

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Project description: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.

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