biostudies-literatureSubhash SVetenskapsrådetSwedish Cancer SocietyBarncancerfondenFoU Västra GötalandsregionenStiftelsen för Strategisk ForskningKnut och Alice Wallenbergs Stiftelse106https://www.ebi.ac.uk/biostudies/studies/S-EPMC5062931biostudies-literatureUnknown8<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.Clinical epigeneticsGlobal DNA methylation profiling reveals new insights into epigenetically deregulated protein coding and long noncoding RNAs in CLL.PMC5062931RB13-0204CAN 2013/386Dnr KAW 2014.0057dnr E 2012/126ALFGBG-507731PR2014/0147Subhash SAndersson POKanduri CKosalai STKanduri MfalseGlobal DNA methylation profiling reveals new insights into epigenetically deregulated protein coding and long noncoding RNAs in CLL.<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.2016-01-01T00:00:00Z20162024-11-12T09:37:22.202Z2019-06-06T16:29:25ZS-EPMC50629312777763510.1186/s13148-016-0274-6