Global Analysis of DNA Methylation by Methyl-Capture Sequencing Reveals Epigenetic change of pancreatic cancer

Purpose: To establish pancreatic cancer-related aberrnat DNA methylation patterns, especially in CGI, CGI shore, orphan CGI and non-CGI promoter region and provide diagnosis or prognosis biomarker for pancreatic cancer dignosis or prognosis prediction Methods:MBD methylCap/seq was carried out to screen differentially methylated CpG islands in 3 libraries which includes 1 pancreatic cancer mix library, 1 adjacent normal tissue mix library and 1 normal pancreas tissue. MSP and multiplex-BSP validation was performed in independent tumor and adjacent tissues. Results: 66807 Hypermethylation DMR and 46815 Hypomethylation DMR were discovered in whole pancreatic cancer genome. 5280 Hypermethylation and 3488 Hypomethylation CpGI region were related gene promoter or gene body. Gene expression of 10 aberrant DMR were related with their methylation status validated by MSRE-qPCR and RT-PCR in 5-aza' treated pancreatic cancer cell line. 40 DMR were validated in pancreatic cancer and adjacent tissues with MSP and gene ontology analysis showed seven of them were related with regulation of transcription(GO:0006355) which included DLX4,ELAVL2,IRX1,PITX2,SIM2,TBX5,TFAP2C. Conclusions: Methylcap-seq identified hundreds of DMR genes and regions which might involve with gene expression regulation and could be used as biological markers of pancreatic cancer therapy target or diagnosis. Overall design: Global Analysis of DNA Methylation by Methyl-CaptureSequencing Reveals Epigenetic change of pancreatic cancer