Similar Datasets
Project description:Intraclonal subpopulations of circulating chronic lymphocytic leukemia (CLL) cells with different proliferative histories and reciprocal surface expression of CXCR4 and CD5 have been observed in the peripheral blood of CLL patients and named proliferative (PF), intermediate (IF), and resting (RF) cellular fractions. Here, we found that these intraclonal circulating fractions share persistent DNA methylation signatures largely associated with the mutation status of the immunoglobulin heavy chain locus (IGHV) and their origins from distinct stages of differentiation of antigen-experienced B cells. Increased leukemic birth rate, however, showed a very limited impact on DNA methylation of circulating CLL fractions independent of IGHV mutation status. Additionally, DNA methylation heterogeneity increased as leukemic cells advanced from PF to RF in the peripheral blood. This frequently co-occurred with heterochromatin hypomethylation and hypermethylation of Polycomb-repressed regions in the PF, suggesting accumulation of longevity-associated epigenetic features in recently born cells. On the other hand, transcriptional differences between paired intraclonal fractions confirmed their proliferative experience and further supported a linear advancement from PF to RF in the peripheral blood. Several of these differentially expressed genes showed unique associations with clinical outcome not evident in the bulk clone, supporting the pathological and therapeutic relevance of studying intraclonal CLL fractions. We conclude that independent methylation and transcriptional landscapes reflect both preexisting cell-of-origin fingerprints and more recently acquired hallmarks associated with the life cycle of circulating CLL cells.
| S-EPMC7065474 | biostudies-literature
Project description:Intraclonal subpopulations of circulating chronic lymphocytic leukemia (CLL) cells with different proliferative histories and reciprocal surface expression of CXCR4 and CD5 have been observed in the peripheral blood of CLL patients and named proliferative (PF), intermediate (IF) and resting (RF) cellular fractions. Here we found that these intraclonal circulating fractions share persistent DNA methylation signatures largely associated with the mutation status of the immunoglobulin heavy chain locus (IGHV) and their origins from distinct stages of differentiation of antigen-experienced B-cells. Increased leukemic birth rate (BR), however, showed a very limited impact on DNA methylation of circulating CLL fractions independent of IGHV mutation status. Additionally, DNA methylation heterogeneity increased as leukemic cells advanced from PF to RF in the peripheral blood. This frequently co-occurred with heterochromatin hypomethylation and hypermethylation of Polycomb-repressed regions in the PF, suggesting accumulation of longevity-associated epigenetic features in recently born cells.
2020-03-16 | GSE144894 | GEO
Project description:Intraclonal subpopulations of circulating chronic lymphocytic leukemia (CLL) cells with different proliferative histories and reciprocal surface expression of CXCR4 and CD5 have been observed in the peripheral blood of CLL patients and named proliferative (PF), intermediate (IF) and resting (RF) cellular fractions. Transcriptional differences between paired intraclonal fractions confirmed their proliferative experience and further supported a linear advancement from PF to RF in the peripheral blood. Marked expression differences in intraclonal fractions suggest potential pathological and therapeutic relevance of studying intraclonal CLL fractions as compared to bulk cells.
2020-03-16 | GSE144896 | GEO
Project description:CLL intraclonal fractions exhibit established and recently-acquired patterns of DNA methylation
| PRJNA605240 | ENA
Project description:CLL intraclonal fractions exhibit established and recently-acquired patterns of DNA methylation [ME]
| PRJNA605239 | ENA
Project description:CLL intraclonal fractions exhibit established and recently-acquired patterns of DNA methylation [GE]
| PRJNA605242 | ENA
Project description:Our findings suggest that gender is underwritten in the epigenome in a tissue-specific manner. Gender-specific epigenetic states are likely to have important implications for understanding sexually dimorphic phenotypes in health and disease.
2017-07-19 | GSE84573 | GEO
Project description:BackgroundSoft tissue sarcomas (STS) are heterogeneous mesenchymal tumors with diverse subtypes. STS can be classified into two main categories according to the type of genomic alteration: recurrent translocation driven STS, and non-recurrent translocations. However, little has known about acquired uniparental disomy in STS.MethodsIn this study, we analyzed SNP microarray data to determine the frequency and distribution patterns of acquired uniparental disomy (aUPD) in major soft tissue sarcoma (STS) subtypes using CNAG and R softwares.ResultsWe identified recurrent aUPD regions specific to alveolar rhabdomyosarcoma with the most frequent at 11p15.4, gastrointestinal stromal tumor at 1p36.11-p35.3, leiomyosarcoma at 17p13.3-p13.1, myxofibrosarcoma at 1p35.1-p34.2 and 16q23.3-q24.1, and pleomorphic liposarcoma at 13q13.2-q13.3 and 13q14.11-q14.2. In contrast, specific recurrent aUPD regions were not identified in dedifferentiated liposarcoma, Ewing sarcoma, myxoid/round cell liposarcoma, and synovial sarcoma. Strikingly total, centromeric and segmental aUPD regions are more frequent in STS that do not exhibit recurrent translocation events.ConclusionsOur study yields a detailed map of aUPD across 9 diverse STS subtypes and suggests the potential location of several novel tumor suppressor genes and oncogenes.
| S-EPMC3541987 | biostudies-literature
Project description:We performed RRBS and WGBS on primary human chronic lymphocytic leukemia and normal healthy donor B cell samples Due to patient privacy concerns, the raw data is being made available via controlled access in dbGaP (http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000435.v1.p1).
2015-01-01 | GSE58889 | GEO
Project description:BackgroundCytosine methylation is a stable epigenetic modification of DNA that plays an important role in both normal physiology and disease. Most diseases exhibit some degree of sexual dimorphism, but the extent to which epigenetic states are influenced by sex is understudied and poorly understood. To address this deficit we studied DNA methylation patterns across multiple reduced representation bisulphite sequencing datasets (from liver, heart, brain, muscle and spleen) derived from isogenic male and female mice.ResultsDNA methylation patterns varied significantly from tissue to tissue, as expected, but they also varied between the sexes, with thousands of sexually dimorphic loci identified. The loci affected were largely autonomous to each tissue, even within tissues derived from the same germ layer. At most loci, differences between genders were driven by females exhibiting hypermethylation relative to males; a proportion of these differences were independent of the presence of testosterone in males. Loci harbouring gender differences were clustered in ontologies related to tissue function.ConclusionsOur findings suggest that gender is underwritten in the epigenome in a tissue-specific and potentially sex hormone-independent manner. Gender-specific epigenetic states are likely to have important implications for understanding sexually dimorphic phenotypes in health and disease.
| S-EPMC5729250 | biostudies-literature