{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Subhash S"],"funding":["Vetenskapsrådet","Swedish Cancer Society","Barncancerfonden","FoU Västra Götalandsregionen","Stiftelsen för Strategisk Forskning","Knut och Alice Wallenbergs Stiftelse"],"pagination":["106"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5062931"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8"],"pubmed_abstract":["<h4>Background</h4>Methyl-CpG-binding domain protein enriched genome-wide sequencing (MBD-Seq) is a robust and powerful method for analyzing methylated CpG-rich regions with complete genome-wide coverage. In chronic lymphocytic leukemia (CLL), the role of CpG methylated regions associated with transcribed long noncoding RNAs (lncRNA) and repetitive genomic elements are poorly understood. Based on MBD-Seq, we characterized the global methylation profile of high CpG-rich regions in different CLL prognostic subgroups based on IGHV mutational status.<h4>Results</h4>Our study identified 5800 hypermethylated and 12,570 hypomethylated CLL-specific differentially methylated genes (cllDMGs) compared to normal controls. From cllDMGs, 40 % of hypermethylated and 60 % of hypomethylated genes were mapped to noncoding RNAs. In addition, we found that the major repetitive elements such as short interspersed elements (SINE) and long interspersed elements (LINE) have a high percentage of cllDMRs (differentially methylated regions) in IGHV subgroups compared to normal controls. Finally, two novel lncRNAs (hypermethylated <i>CRNDE</i> and hypomethylated <i>AC012065.7</i>) were validated in an independent CLL sample cohort (48 samples) compared with 6 normal sorted B cell samples using quantitative pyrosequencing analysis. The methylation levels showed an inverse correlation to gene expression levels analyzed by real-time quantitative PCR. Notably, survival analysis revealed that hypermethylation of <i>CRNDE</i> and hypomethylation of <i>AC012065.7</i> correlated with an inferior outcome.<h4>Conclusions</h4>Thus, our comprehensive methylation analysis by MBD-Seq provided novel hyper and hypomethylated long noncoding RNAs, repetitive elements, along with protein coding genes as potential epigenetic-based CLL-signature genes involved in disease pathogenesis and prognosis."],"journal":["Clinical epigenetics"],"pubmed_title":["Global DNA methylation profiling reveals new insights into epigenetically deregulated protein coding and long noncoding RNAs in CLL."],"pmcid":["PMC5062931"],"funding_grant_id":["RB13-0204","CAN 2013/386","Dnr KAW 2014.0057","dnr E 2012/126","ALFGBG-507731","PR2014/0147"],"pubmed_authors":["Subhash S","Andersson PO","Kanduri C","Kosalai ST","Kanduri M"],"additional_accession":[]},"is_claimable":false,"name":"Global DNA methylation profiling reveals new insights into epigenetically deregulated protein coding and long noncoding RNAs in CLL.","description":"<h4>Background</h4>Methyl-CpG-binding domain protein enriched genome-wide sequencing (MBD-Seq) is a robust and powerful method for analyzing methylated CpG-rich regions with complete genome-wide coverage. In chronic lymphocytic leukemia (CLL), the role of CpG methylated regions associated with transcribed long noncoding RNAs (lncRNA) and repetitive genomic elements are poorly understood. Based on MBD-Seq, we characterized the global methylation profile of high CpG-rich regions in different CLL prognostic subgroups based on IGHV mutational status.<h4>Results</h4>Our study identified 5800 hypermethylated and 12,570 hypomethylated CLL-specific differentially methylated genes (cllDMGs) compared to normal controls. From cllDMGs, 40 % of hypermethylated and 60 % of hypomethylated genes were mapped to noncoding RNAs. In addition, we found that the major repetitive elements such as short interspersed elements (SINE) and long interspersed elements (LINE) have a high percentage of cllDMRs (differentially methylated regions) in IGHV subgroups compared to normal controls. Finally, two novel lncRNAs (hypermethylated <i>CRNDE</i> and hypomethylated <i>AC012065.7</i>) were validated in an independent CLL sample cohort (48 samples) compared with 6 normal sorted B cell samples using quantitative pyrosequencing analysis. The methylation levels showed an inverse correlation to gene expression levels analyzed by real-time quantitative PCR. Notably, survival analysis revealed that hypermethylation of <i>CRNDE</i> and hypomethylation of <i>AC012065.7</i> correlated with an inferior outcome.<h4>Conclusions</h4>Thus, our comprehensive methylation analysis by MBD-Seq provided novel hyper and hypomethylated long noncoding RNAs, repetitive elements, along with protein coding genes as potential epigenetic-based CLL-signature genes involved in disease pathogenesis and prognosis.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016","modification":"2024-11-12T09:37:22.202Z","creation":"2019-06-06T16:29:25Z"},"accession":"S-EPMC5062931","cross_references":{"pubmed":["27777635"],"doi":["10.1186/s13148-016-0274-6"]}}