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  • 1
    Keywords: CANCER ; EXPRESSION ; Germany ; GENE ; GENES ; DNA ; TARGET ; CHROMATIN ; PROMOTER ; inactivation ; POOR-PROGNOSIS ; HYPERMETHYLATION ; FEATURES ; ONCOLOGY ; PROFILES ; SEPARATION ; B-CELL ; POLYCOMB ; PRINCIPAL-COMPONENTS-ANALYSIS
    Abstract: Background: Although primary lymphomas of the central nervous system (PCNSL) and extracerebral diffuse large B-cell lymphoma (DLBCL) cannot be distinguished histologically, it is still a matter of debate whether PCNSL differ from systemic DLBCL with respect to their molecular features and pathogenesis. Analysis of the DNA methylation pattern might provide further data distinguishing these entities at a molecular level. Methods: Using an array-based technology we have assessed the DNA methylation status of 1,505 individual CpG loci in five PCNSL and compared the results to DNA methylation profiles of 49 DLBCL and ten hematopoietic controls. Results: We identified 194 genes differentially methylated between PCNSL and normal controls. Interestingly, Polycomb target genes and genes with promoters showing a high CpG content were significantly enriched in the group of genes hypermethylated in PCNSL. However, PCNSL and systemic DLBCL did not differ in their methylation pattern. Conclusions: Based on the data presented here, PCNSL and DLBCL do not differ in their DNA methylation pattern. Thus, DNA methylation analysis does not support a separation of PCNSL and DLBCL into individual entities. However, PCNSL and DLBCL differ in their DNA methylation pattern from non-malignant controls
    Type of Publication: Journal article published
    PubMed ID: 20025734
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  • 2
    Keywords: CELLS ; EXPRESSION ; CELL ; Germany ; human ; GENE ; GENES ; DIFFERENTIATION ; DNA ; TISSUES ; LYMPHOMA ; PATTERNS ; DNA methylation ; TARGETS ; INSIGHTS ; METHYLATION ; B-CELL LYMPHOMA ; DE-NOVO METHYLATION ; EMBRYONIC STEM-CELLS ; HUMAN CANCER ; development ; non-Hodgkin lymphoma ; BURKITTS-LYMPHOMA ; HEMATOPOIETIC TISSUES ; DEFINED FACTORS ; DEVELOPMENTAL REGULATORS ; INSTRUCTIVE MECHANISM
    Abstract: Lymphomas are assumed to originate at different stages of lymphocyte development through chromosomal aberrations. Thus, different lymphomas resemble lymphocytes at distinct differentiation stages and show characteristic morphologic, genetic, and transcriptional features. Here, we have performed a microarray-based DNA methylation profiling of 83 mature aggressive B-cell non-Hodgkin lymphomas (maB-NHLs) characterized for their morphologic, genetic, and transcriptional features, including molecular Burkitt lymphomas and diffuse large B-cell lymphomas. Hierarchic clustering indicated that methylation patterns in maB-NHLs were not strictly associated with morphologic, genetic, or transcriptional features. By supervised analyses, we identified 56 genes de novo methylated in all lymphoma subtypes studied and 22 methylated in a lymphoma subtype-specific manner. Remarkably, the group of genes de novo methylated in all lymphoma subtypes was significantly enriched for polycomb targets in embryonic stem cells. De novo methylated genes in all maB-NHLs studied were expressed at low levels in lymphomas and normal hematopoietic tissues but not in nonhematopoietic tissues. These findings, especially the enrichment for polycomb targets in stem cells, indicate that maB-NHLs with different morphologic, genetic, and transcriptional background share a similar stem cell-like epigenetic pattern. This suggests that maB-NHLs originate from cells with stem cell features or that stemness was acquired during lymphomagenesis by epigenetic remodeling. (Blood. 2009;113:2488-2497)
    Type of Publication: Journal article published
    PubMed ID: 19075189
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