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Series GSE21304 Query DataSets for GSE21304
Status Public on Oct 18, 2010
Title Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of human multiple myeloma
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary We have used genome-wide methylation microarrays to analyze differences in CpG methylation patterns in cells relevant to the pathogenesis of myeloma plasma cells, including B cells, normal plasma cells, MGUS, presentation myeloma, and plasma cell leukemia (PCL). We show that methylation patterns in these cell types are capable of distinguishing non-malignant from malignant cells and that the main reason for this difference is hypomethylation of the genome at the transition from MGUS to presentation myeloma. In addition, gene-specific hypermethylation was evident at the myeloma stage. Differential methylation was also evident at the transition from myeloma to PCL with re-methylation of the genome, specifically of genes involved in cell-cell signaling and cell adhesion, which may contribute to independence from the bone marrow microenvironment. There was a high degree of methylation variability within presentation myeloma samples and this was associated with the cytogenetic differences between samples. More specifically, we found that methylation subgroups were defined by translocations and hyperdiploidy, with t(4;14) myeloma having the largest impact on DNA methylation. Two groups of hyperdiploid samples were identified, based on unsupervised clustering, which had an impact on overall survival. Overall, DNA methylation has a large impact on disease progression and on myeloma cytogenetic subgroups.
 
Overall design Bone marrow aspirates were obtained after informed consent. B cells (n=6) from normal individuals were selected from peripheral blood using CD19. Plasma cells (PC) from non-myeloma patients (normal plasma cell controls, n=3) as well as MGUS (n=4) and presentation myeloma patients (n=161) were selected to a purity of >90% using CD138 microbeads and magnet-assisted cell sorting (Miltenyi Biotech, Bisley, UK). Samples from PCL patients (n=7) were not CD138 selected but contained >90% plasma cell infiltration as determined by microscopy. In order to achieve a sufficient quantity of DNA some normal plasma cell control samples were pooled.
 
Contributor(s) Walker BA, Morgan GJ
Citation(s) 20944071, 23699600
Submission date Apr 12, 2010
Last update date Jan 02, 2015
Contact name Brian A Walker
E-mail(s) brian.walker@icr.ac.uk
Organization name The Institute of Cancer Research
Department Haemato-Oncology Research Unit
Lab Molecular Haematology Team
Street address 15 Cotswold Road
City Sutton
ZIP/Postal code SM2 5NG
Country United Kingdom
 
Platforms (1)
GPL8490 Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2)
Samples (190)
GSM532360 Bcell-1
GSM532361 Bcell-2
GSM532362 Bcell-3
Relations
BioProject PRJNA126573

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE21304_RAW.tar 5.8 Mb (http)(custom) TAR
Processed data not applicable for this record

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