Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma

Walker, Brian A., Wardell, Chrostopher P., Chiecchio, Laura, Smith, Emma M., Boyd, Kevin D., Neri, Antonio, Davies, Faith E., Ross, Fiona M. and Morgan, Gareth J. (2010) Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma Blood, 117, (2), pp. 553-562. (doi:10.1182/blood-2010-04-279539). (PMID:20944071).


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We used genome-wide methylation microarrays to analyze differences in CpG methylation patterns in cells relevant to the pathogenesis of myeloma plasma cells (B cells, normal plasma cells, monoclonal gammopathy of undetermined significance [MGUS], presentation myeloma, and plasma cell leukemia). We show that methylation patterns in these cell types are capable of distinguishing nonmalignant from malignant cells and 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 plasma cell leukemia with remethylation of the genome, particularly 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, which was associated with cytogenetic differences between samples. More specifically, we found methylation subgroups were defined by translocations and hyperdiploidy, with t(4;14) myeloma having the greatest impact on DNA methylation. Two groups of hyperdiploid samples were identified, on the basis of unsupervised clustering, which had an impact on overall survival. Overall, DNA methylation changes significantly during disease progression and between cytogenetic subgroups

Item Type: Article
Digital Object Identifier (DOI): doi:10.1182/blood-2010-04-279539
ISSNs: 0006-4971 (print)
Organisations: Human Development & Health
ePrint ID: 337719
Date :
Date Event
13 October 2010e-pub ahead of print
13 January 2011Published
Date Deposited: 02 May 2012 14:16
Last Modified: 17 Apr 2017 17:14
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/337719

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