中文摘要：

目的 建立骨髓增生异常综合征（MDS）的CpG岛甲基化模式,为MDS的早期诊断和鉴别诊断提供新的生物学标志.方法 采用Illumina450k甲基化芯片和Agilent全基因组表达谱基因芯片进行差异基因筛选,筛选出高甲基化低表达基因,初步建立MDS的CpG岛甲基化模式.通过甲基化特异性PCR、重硫酸盐测序和实时荧光定量PCR进一步在MDS患者组及对照组（非恶性血液病患者）中进行验证,最终建立CpG岛甲基化模式.最后采用诊断试验评价的方法评价CpG岛甲基化模式诊断MDS的效能.结果 通过甲基化芯片和表达谱基因芯片的关联分析,以及在211例MDS患者组和60例对照组中进行验证,建立的MDS CpG岛甲基化模式为高甲基化低表达的6个基因.6个基因在MDS组发生甲基化的比例分别为ABAT （97％）、DAPP1 （98％）、FADD（89％）、LRRFIP1 （96％）、PLBD1 （89％）和SMPD3 （85％）.5个或5个以上基因同时发生甲基化时诊断MDS的特异度和灵敏度为95.0％和91.4％,准确度为92.3％.结论 由ABAT、DAPP1、FADD、LRRFIP1、PLBD1、SMPD3这6个基因建立的MDS的CpG岛甲基化模式可以提高MDS诊断的准确性及鉴别诊断效能.

英文摘要：

Objective To identify methylation profiles in myelodysplastic syndrome （MDS） and to provide the biomarkers for the early diagnosis and differential diagnosis of MDS. Methods Genes were screened for hypermethylation by genome-wide DNA methylation profiles. Transcription down-regnlation was determined with a gene expression microarray. Methylation-specific, real-time, and bisulfite- sequencing PCR cloning and sequencing were performed to validate selected genes in MDS cases and non- malignant hematologic diseases （controls）. Diagnostic test, such as sensitivity and specificity, was used to evaluate the value of methylation patterns. Results A draft of methylation patterns was established and refined to 6 genes after validation in 211 patients and 60 controls. The hypermethylated genes were ABAT （97%）, DAPP1 （98%）, FADD （89%）, LRRFIP1 （96%）, PLBD1 （89%）, and SMPD3 （85%）. A combination of 5 or more than 5 genes showed a specificity of 95% and sensitivity of 91.4% for the diagnosis of MDS. The accuracy of diagnosis was 92.3%. Conclusions We demonstrated here that the ABAT, DAPPI, FADD, LRRFIP1, PLBD1 and SMPD3 genes are hypermethylated and downregulated in MDS. The six genes could be the markers of the methylation patterns in MDS, as a noninvasive approach for the diagnosis of MDS.