DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



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

Author(s): Walker BA, Wardell CP, Chiecchio L, Smith EM, Boyd KD, Neri A, Davies FE, Ross FM, Morgan GJ

Affiliation(s): The Institute of Cancer Research, London, UK. brian.walker@icr.ac.uk

Publication date & source: 2011-01-13, Blood., 117(2):553-62. Epub 2010 Oct 13.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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.

Page last updated: 2011-12-09

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017