PMBCL IL4R DASL
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00010001542 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Primary mediastinal B-cell lymphoma (PMBCL) is a distinct subtype of diffuse large B-cell lymphoma. PMBCL has been previously studied with a variety of genomic techniques resulting in frequent detection of chromosomal gains; however, chromosomal losses have been rarely reported. This finding contrasts many other types of lymphoma, in which deletions are common. We hypothesize that segmental losses do exist but may have escaped detection by methods used in the previous studies. Using array comparative genomic hybridization to a tiling-resolution microarray encompassing the entire human genome, PMBCL samples were analyzed for genomic copy number alterations. Both gains and losses of chromosomal material were detected throughout the genome. These DNA copy number alterations were confirmed by quantitative real-time PCR. Recurrent chromosomal losses include a novel event at 1p13.1-p13.2 present in 42% of cases analyzed. We conclude that losses are present in the PMBCL genome. Given the similar frequency of losses to that of segmental gains of DNA, they are likely to play an important role in the pathogenesis of PMBCL. Keywords: array CGH, PMBCL
2007-08-15 | GSE7383 | GEO
Project description:Primary mediastinal B-cell lymphoma (PMBCL) is a distinct subtype of diffuse large B-cell lymphoma. PMBCL has been previously studied with a variety of genomic techniques resulting in frequent detection of chromosomal gains; however, chromosomal losses have been rarely reported. This finding contrasts many other types of lymphoma, in which deletions are common. We hypothesize that segmental losses do exist but may have escaped detection by methods used in the previous studies. Using array comparative genomic hybridization to a tiling-resolution microarray encompassing the entire human genome, PMBCL samples were analyzed for genomic copy number alterations. Both gains and losses of chromosomal material were detected throughout the genome. These DNA copy number alterations were confirmed by quantitative real-time PCR. Recurrent chromosomal losses include a novel event at 1p13.1-p13.2 present in 42% of cases analyzed. We conclude that losses are present in the PMBCL genome. Given the similar frequency of losses to that of segmental gains of DNA, they are likely to play an important role in the pathogenesis of PMBCL. Whole genome tiling path array CGH of 20 PMBCL tumor samples and one cell line was performed against male reference genomic DNA. Alterations were confirmed via DNA copy number quantitative real-time PCR
2007-08-15 | E-GEOD-7383 | biostudies-arrayexpress
Project description:Primary mediastinal large B cell lymphoma (PMBCL) is a distinct subtype of diffuse large B cell lymphoma thought to arise from thymic medullary B cells. Gene mutations underlying the molecular pathogenesis of the disease are incompletely characterized. Here, we describe novel somatic IL4R mutations in 15 out of 62 primary cases of PMBCL (24.2%) and in all PMBCL-derived cell lines tested. The majority of mutations (11/21; 52%) were hotspot single nucleotide variants in exon 8 leading to an I242N amino acid change in the transmembrane domain. Functional analyses establish this mutation as gain-of-function leading to constitutive activation of the JAK-STAT pathway and upregulation of downstream cytokine expression profiles and B cell specific antigens. Moreover, expression of I242N mutant IL4R in a mouse xenotransplantation model conferred growth advantage in vivo. The pattern of concurrent mutations within the JAK-STAT signaling pathway suggests additive/synergistic effects of these gene mutations contributing to lymphomagenesis. Our data establish IL4R mutations as novel driver alterations and provide a strong preclinical rationale for therapeutic targeting of JAK-STAT signaling in PMBCL.
| EGAS00001002796 | EGA
Project description:Recent exome-wide studies discovered frequent somatic mutations in the epigenetic modifier ZNF217 in primary mediastinal B cell lymphoma (PMBCL) and related disorders. As functional consequences of ZNF217 alterations remain unknown, we comprehensively evaluated their impact in PMBCL. Targeted sequencing identified genetic lesions affecting ZNF217 in 33% of 157 PMBCL patients. Subsequent gene expression profiling (n=120) revealed changes in cytokine and interferon signal transduction in ZNF217-aberrant PMBCL cases. In vitro, knockout of ZNF217 led to changes in chromatin accessibility interfering with binding motifs for crucial lymphoma-associated transcription factors. This led to disturbed expression of interferon-responsive and inflammation-associated genes, altered cell behavior, and an activated B cell phenotype. Mass spectrometry demonstrates that ZNF217 acts within a histone modifier complex containing LSD1, CoREST and HDAC and interferes with H3K4 methylation and H3K27 acetylation. Concluding, our data suggest non-catalytic activity of ZNF217, which directs histone modifier complex function and controls B cell differentiation-associated patterns of chromatin structure.
2024-01-26 | PXD040928 | Pride
Project description:Recent exome-wide studies discovered frequent somatic mutations in the epigenetic modifier ZNF217 in primary mediastinal B cell lymphoma (PMBCL) and related disorders. As functional consequences of ZNF217 alterations remain unknown, we comprehensively evaluated their impact in PMBCL. Targeted sequencing identified genetic lesions affecting ZNF217 in 33% of 157 PMBCL patients. Subsequent gene expression profiling (n=120) revealed changes in cytokine and interferon signal transduction in ZNF217-aberrant PMBCL cases. In vitro, knockout of ZNF217 led to changes in chromatin accessibility interfering with binding motifs for crucial lymphoma-associated transcription factors. This led to disturbed expression of interferon-responsive and inflammation-associated genes, altered cell behavior, and an activated B cell phenotype. Mass spectrometry demonstrates that ZNF217 acts within a histone modifier complex containing LSD1, CoREST and HDAC and interferes with H3K4 methylation and H3K27 acetylation. Concluding, our data suggest non-catalytic activity of ZNF217, which directs histone modifier complex function and controls B cell differentiation-associated patterns of chromatin structure.
2024-01-26 | PXD034337 | Pride
Project description:Microarrays displaying zebrafish miRNAs specific probes were hybridized using RNA samples originating from whole body homogenates of male zebrafish exposed to 17-beta estradiol (E2) for 0, 1, 4. 12 and 24 hours. 0 hr fish No. 40, 41, 42. 1hr fish No. 8, 10, 11. 4hr fish No. 19, 20, 23. 12hr fish No. 24, 25, 26. 24hr fish No. 29, 31, 32. <br><br> The hybridizations used in these experiments: Chip 1: 10-42, Chip 2: 40-8, Chip 3: 41-11, Chip 4: 42-19, Chip 5: 20-40, Chip 6: 23-41, Chip 7: 25-42, Chip 8: 40-24, Chip 9: 41-26, Chip 10: 42-29, Chip 11: 31-40, Chip 12: 32-41
2007-12-30 | E-MEXP-1147 | biostudies-arrayexpress
Project description:The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information. We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n=32) and gene expression (n=36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n=25) had an increased risk of recurrence as a first event (p=0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26-16.0) and death (p=0.04, HR, 4.95; 95% CI, 1.36-31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p=0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes. This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker. 32 tumour samples were profiled by aCGH, in 2-colour hybridisations with common pooled unrelated normal genomic DNA in the reference channel. There were no replicates.
2014-08-30 | E-GEOD-60852 | biostudies-arrayexpress
Project description:We previously identified rearrangements involving CIITA, the master transcriptional regulator of MHC class II expression, as common mutational events in PMBCL and cHL. In order to inform on the prevalence and different types of structural genomic aberrations affecting CIITA in PMBCL and HL we performed high-resolution copy number analysis. Affymetrix SNP6 arrays were performed according to the manufacturer's instructions on DNA extracted from cell lines.
2015-10-12 | GSE73558 | GEO
Project description:Several DNA sequencing studies of chronic lymphocytic leukemia (CLL) revealed that the splicing factor SF3B1 accumulated somatic point mutations in about 10 percent of the patients. In most cases the mutations were located in the genomic regions coding for the C-terminal HEAT-repeat domain and in many cases, the mutations gave rise to specific amino acid substitutions. Here, we aimed to investigate differential usage of exons associated with the mutation K700E of SF3B1 in CLL tumuor cells. We generated RNA-Seq transcriptome data from two patients with mutations in SF3B1, two patient without mutations in SF3B1 and from healthy donors. We report interesting examples and possible consequences of the alternative exon usage in these genes. This dataset contains only the files resulting from the processing the RNA sequencing raw data. This avoids potential patient identifiability, but ensures the full reproducibility of the results described in the publication.
2013-12-27 | E-MTAB-2025 | biostudies-arrayexpress
Project description:- Six samples from the DEV cell line: 2 controls, 2 transduced with IL4R WT and 2 transduced with IL4R mutant (I242N)
- This DEV cell line is not commercially available and was acquired from a colleague in the Netherlands
| EGAD00001003908 | EGA