Whole genome methylation profiles of myelodysplastic syndrome and its diagnostic value

Abstract

To identify methylation profiles in myelodysplastic syndrome (MDS) and to provide the biomarkers for the early diagnosis and differential diagnosis of MDS. Genes were screened for hypermethylation by genome-wide DNA methylation profiles. Transcription down-regulation 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. 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%. We demonstrated here that the ABAT, DAPP1, 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.