黑色素瘤中的DNA甲基化亚组与增殖和免疫过程相关。
DNA methylation subgroups in melanoma are associated with proliferative and immunological processes.
作者信息
Lauss Martin, Ringnér Markus, Karlsson Anna, Harbst Katja, Busch Christian, Geisler Jürgen, Lønning Per Eystein, Staaf Johan, Jönsson Göran
机构信息
Department of Oncology and Pathology, Clinical Sciences, Lund University Hospital, Lund University, Lund, 221 85, Sweden.
Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.
出版信息
BMC Med Genomics. 2015 Nov 6;8:73. doi: 10.1186/s12920-015-0147-4.
BACKGROUND
DNA methylation at CpG dinucleotides is modified in tumorigenesis with potential impact on transcriptional activity.
METHODS
We used the Illumina 450 K platform to evaluate DNA methylation patterns of 50 metastatic melanoma tumors, with matched gene expression data.
RESULTS
We identified three different methylation groups and validated the groups in independent data from The Cancer Genome Atlas. One group displayed hypermethylation of a developmental promoter set, genome-wide demethylation, increased proliferation and activity of the SWI/SNF complex. A second group had a methylation pattern resembling stromal and leukocyte cells, over-expressed an immune signature and had improved survival rates in metastatic tumors (p < 0.05). A third group had intermediate methylation levels and expressed both proliferative and immune signatures. The methylation groups corresponded to some degree with previously identified gene expression phenotypes.
CONCLUSIONS
Melanoma consists of divergent methylation groups that are distinguished by promoter methylation, proliferation and content of immunological cells.
背景
在肿瘤发生过程中，CpG二核苷酸处的DNA甲基化会发生改变，这可能对转录活性产生影响。
方法
我们使用Illumina 450K平台评估了50例转移性黑色素瘤肿瘤的DNA甲基化模式，并匹配了基因表达数据。
结果
我们识别出三个不同的甲基化组，并在来自癌症基因组图谱的独立数据中验证了这些组。一组表现出发育启动子集的高甲基化、全基因组去甲基化、SWI/SNF复合物增殖和活性增加。第二组的甲基化模式类似于基质细胞和白细胞，过度表达免疫特征，转移性肿瘤的生存率提高（p<0.05）。第三组具有中等甲基化水平，同时表达增殖和免疫特征。甲基化组在一定程度上与先前确定的基因表达表型相对应。
结论
黑色素瘤由不同的甲基化组组成，这些组通过启动子甲基化、增殖和免疫细胞含量来区分。
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