期刊
BLOOD
卷 117, 期 2, 页码 553-562出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-04-279539
关键词
-
类别
资金
- Cancer Research UK
- Bud Flanagan Research Fund
- Leukemia Research Fund
- United Kingdom Department of Health
- Myeloma UK
- Associazione Italiana Ricerca sul Cancro
- Biological Research Center of the National Institute for Health Research at the Royal Marsden Hospital
- MRC [G0100132] Funding Source: UKRI
- Medical Research Council [G0100132] Funding Source: researchfish
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 be-tween 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. (Blood. 2011; 117(2):553-562)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据