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

Brian A. Walker, Christopher P. Wardell, Laura Chiecchio, Emma M. Smith, Kevin D. Boyd, Antonino Neri, Faith E. Davies, Fiona M. Ross, Gareth J. Morgan

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)553-562
Number of pages10
JournalBlood
Volume117
Issue number2
DOIs
Publication statusPublished - Jan 13 2011

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Methylation
Multiple Myeloma
Genes
Plasma Cell Leukemia
Monoclonal Gammopathy of Undetermined Significance
Plasmas
Polyploidy
Genome
DNA Methylation
Cytogenetics
Cell signaling
Cell adhesion
Microarray Analysis
Microarrays
Plasma Cells
Cell Adhesion
Cluster Analysis
Disease Progression
Bone
B-Lymphocytes

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Walker, B. A., Wardell, C. P., Chiecchio, L., Smith, E. M., Boyd, K. D., Neri, A., ... Morgan, G. J. (2011). Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma. Blood, 117(2), 553-562. https://doi.org/10.1182/blood-2010-04-279539

Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma. / Walker, Brian A.; Wardell, Christopher P.; Chiecchio, Laura; Smith, Emma M.; Boyd, Kevin D.; Neri, Antonino; Davies, Faith E.; Ross, Fiona M.; Morgan, Gareth J.

In: Blood, Vol. 117, No. 2, 13.01.2011, p. 553-562.

Research output: Contribution to journalArticle

Walker, BA, Wardell, CP, Chiecchio, L, Smith, EM, Boyd, KD, Neri, A, Davies, FE, Ross, FM & Morgan, GJ 2011, 'Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma', Blood, vol. 117, no. 2, pp. 553-562. https://doi.org/10.1182/blood-2010-04-279539
Walker, Brian A. ; Wardell, Christopher P. ; Chiecchio, Laura ; Smith, Emma M. ; Boyd, Kevin D. ; Neri, Antonino ; Davies, Faith E. ; Ross, Fiona M. ; Morgan, Gareth J. / Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma. In: Blood. 2011 ; Vol. 117, No. 2. pp. 553-562.
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