DNA-DEPENDENT TRANSCRIPTIONAL REGULATORY GENES WERE HYPOMETHYLATED IN KOREAN CHRONIC LYMPHOCYTIC LEUKEMIA – A METHYLCPG BINDING DOMAIN NGS STUDY
(Abstract release date: 05/19/16)
EHA Library. Lee Y. 06/09/16; 132598; E1049
Prof. Dr. Young Kyung Lee
Contributions
Contributions
Abstract
Abstract: E1049
Type: Eposter Presentation
Background
Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in Western countries, but it is very rare and shows relatively poor prognosis in Asian countries including Korea.
Aims
To investigate the differences in the pathobiology of Korean CLL, we analyzed the methylation profile and the expected affected pathways using the methylCpG binding domain NGS (MBD-seq).
Methods
Bone marrow aspirate of 9 CLLs and 5 control individuals were used for MBD-seq using MethylMiner Methylated DNA Enrichment Kit and Illumina Hi-Seq 2000. Differentially methylated regions (DMRs) were determined by filtering for each regions associated with |log2FC|≥1 and exact test p-values<0.05. Hierarchical clustering analysis, gene-enrichment and functional annotation analysis was performed.
Results
Pair-wise correlation coefficient matrix showed a high similarity was observed among either CLL group or control group, but not between the CLL group and the control group. Among 79,612 tested regions regarding to 18,434 genes with CpG islands, CLL group showed 2,078 DMRs (780 genes) – 1,083 hypermethylated regions (350 genes) vs. 995 hypomethylated regions (430 genes). In CpG islands analysis, the DMR profiling clearly separated CLL group from control group. The most frequently hypermethylated genes included ANKRD20A2, CHERP, PRPF38A, C1orf123, FKTN, TRAFD1, SH3D21, MGAT1, NECAB3 and UCKL1. Gene ontology analysis showed genes related with protein localization, cellular macromolecule localization and protein transport were hypermethylated. The most frequently hypomethylated genes included CBX4, OSR2, LMX1B TNRC18, ICAM5, GATA6, CDX2, NR3C2, STK3 and HOXB8. Gene ontology analysis showed genes related DNA dependent transcriptional regulation and RNA metabolic process regulation were hypomethylated. Pathway analysis showed genes related pathways in cancer or hedgehog signaling pathway were hypomethylated.
Conclusion
We performed the whole genome methylation profile analysis using NGS MBD-seq in Korean CLL for the first time. Our result demonstrated that Korean CLL has a distinct methylation profile. Genes related with protein localization, cellular macromolecule localization and protein transport were hypermethylated, and genes related DNA dependent transcriptional regulation and RNA metabolic process regulation were hypomethylated. Cancer pathway and hedgehog signaling pathway could be overexpressed due to hypomethylation in relevant genes.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Methylation
Type: Eposter Presentation
Background
Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in Western countries, but it is very rare and shows relatively poor prognosis in Asian countries including Korea.
Aims
To investigate the differences in the pathobiology of Korean CLL, we analyzed the methylation profile and the expected affected pathways using the methylCpG binding domain NGS (MBD-seq).
Methods
Bone marrow aspirate of 9 CLLs and 5 control individuals were used for MBD-seq using MethylMiner Methylated DNA Enrichment Kit and Illumina Hi-Seq 2000. Differentially methylated regions (DMRs) were determined by filtering for each regions associated with |log2FC|≥1 and exact test p-values<0.05. Hierarchical clustering analysis, gene-enrichment and functional annotation analysis was performed.
Results
Pair-wise correlation coefficient matrix showed a high similarity was observed among either CLL group or control group, but not between the CLL group and the control group. Among 79,612 tested regions regarding to 18,434 genes with CpG islands, CLL group showed 2,078 DMRs (780 genes) – 1,083 hypermethylated regions (350 genes) vs. 995 hypomethylated regions (430 genes). In CpG islands analysis, the DMR profiling clearly separated CLL group from control group. The most frequently hypermethylated genes included ANKRD20A2, CHERP, PRPF38A, C1orf123, FKTN, TRAFD1, SH3D21, MGAT1, NECAB3 and UCKL1. Gene ontology analysis showed genes related with protein localization, cellular macromolecule localization and protein transport were hypermethylated. The most frequently hypomethylated genes included CBX4, OSR2, LMX1B TNRC18, ICAM5, GATA6, CDX2, NR3C2, STK3 and HOXB8. Gene ontology analysis showed genes related DNA dependent transcriptional regulation and RNA metabolic process regulation were hypomethylated. Pathway analysis showed genes related pathways in cancer or hedgehog signaling pathway were hypomethylated.
Conclusion
We performed the whole genome methylation profile analysis using NGS MBD-seq in Korean CLL for the first time. Our result demonstrated that Korean CLL has a distinct methylation profile. Genes related with protein localization, cellular macromolecule localization and protein transport were hypermethylated, and genes related DNA dependent transcriptional regulation and RNA metabolic process regulation were hypomethylated. Cancer pathway and hedgehog signaling pathway could be overexpressed due to hypomethylation in relevant genes.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Methylation
Abstract: E1049
Type: Eposter Presentation
Background
Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in Western countries, but it is very rare and shows relatively poor prognosis in Asian countries including Korea.
Aims
To investigate the differences in the pathobiology of Korean CLL, we analyzed the methylation profile and the expected affected pathways using the methylCpG binding domain NGS (MBD-seq).
Methods
Bone marrow aspirate of 9 CLLs and 5 control individuals were used for MBD-seq using MethylMiner Methylated DNA Enrichment Kit and Illumina Hi-Seq 2000. Differentially methylated regions (DMRs) were determined by filtering for each regions associated with |log2FC|≥1 and exact test p-values<0.05. Hierarchical clustering analysis, gene-enrichment and functional annotation analysis was performed.
Results
Pair-wise correlation coefficient matrix showed a high similarity was observed among either CLL group or control group, but not between the CLL group and the control group. Among 79,612 tested regions regarding to 18,434 genes with CpG islands, CLL group showed 2,078 DMRs (780 genes) – 1,083 hypermethylated regions (350 genes) vs. 995 hypomethylated regions (430 genes). In CpG islands analysis, the DMR profiling clearly separated CLL group from control group. The most frequently hypermethylated genes included ANKRD20A2, CHERP, PRPF38A, C1orf123, FKTN, TRAFD1, SH3D21, MGAT1, NECAB3 and UCKL1. Gene ontology analysis showed genes related with protein localization, cellular macromolecule localization and protein transport were hypermethylated. The most frequently hypomethylated genes included CBX4, OSR2, LMX1B TNRC18, ICAM5, GATA6, CDX2, NR3C2, STK3 and HOXB8. Gene ontology analysis showed genes related DNA dependent transcriptional regulation and RNA metabolic process regulation were hypomethylated. Pathway analysis showed genes related pathways in cancer or hedgehog signaling pathway were hypomethylated.
Conclusion
We performed the whole genome methylation profile analysis using NGS MBD-seq in Korean CLL for the first time. Our result demonstrated that Korean CLL has a distinct methylation profile. Genes related with protein localization, cellular macromolecule localization and protein transport were hypermethylated, and genes related DNA dependent transcriptional regulation and RNA metabolic process regulation were hypomethylated. Cancer pathway and hedgehog signaling pathway could be overexpressed due to hypomethylation in relevant genes.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Methylation
Type: Eposter Presentation
Background
Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in Western countries, but it is very rare and shows relatively poor prognosis in Asian countries including Korea.
Aims
To investigate the differences in the pathobiology of Korean CLL, we analyzed the methylation profile and the expected affected pathways using the methylCpG binding domain NGS (MBD-seq).
Methods
Bone marrow aspirate of 9 CLLs and 5 control individuals were used for MBD-seq using MethylMiner Methylated DNA Enrichment Kit and Illumina Hi-Seq 2000. Differentially methylated regions (DMRs) were determined by filtering for each regions associated with |log2FC|≥1 and exact test p-values<0.05. Hierarchical clustering analysis, gene-enrichment and functional annotation analysis was performed.
Results
Pair-wise correlation coefficient matrix showed a high similarity was observed among either CLL group or control group, but not between the CLL group and the control group. Among 79,612 tested regions regarding to 18,434 genes with CpG islands, CLL group showed 2,078 DMRs (780 genes) – 1,083 hypermethylated regions (350 genes) vs. 995 hypomethylated regions (430 genes). In CpG islands analysis, the DMR profiling clearly separated CLL group from control group. The most frequently hypermethylated genes included ANKRD20A2, CHERP, PRPF38A, C1orf123, FKTN, TRAFD1, SH3D21, MGAT1, NECAB3 and UCKL1. Gene ontology analysis showed genes related with protein localization, cellular macromolecule localization and protein transport were hypermethylated. The most frequently hypomethylated genes included CBX4, OSR2, LMX1B TNRC18, ICAM5, GATA6, CDX2, NR3C2, STK3 and HOXB8. Gene ontology analysis showed genes related DNA dependent transcriptional regulation and RNA metabolic process regulation were hypomethylated. Pathway analysis showed genes related pathways in cancer or hedgehog signaling pathway were hypomethylated.
Conclusion
We performed the whole genome methylation profile analysis using NGS MBD-seq in Korean CLL for the first time. Our result demonstrated that Korean CLL has a distinct methylation profile. Genes related with protein localization, cellular macromolecule localization and protein transport were hypermethylated, and genes related DNA dependent transcriptional regulation and RNA metabolic process regulation were hypomethylated. Cancer pathway and hedgehog signaling pathway could be overexpressed due to hypomethylation in relevant genes.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Methylation
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