A unique feature of the tumour cells (Hodgkin/Reed-Sternberg (HRS)) of classical Hodgkin lymphoma (cHL) is the loss of their B-cell phenotype despite their B-cell origin. Several lines of evidence suggest that epigenomic events, especially promoter DNA-methylation, are involved in this silencing of many B-cell associated genes. Here we show that DNA-demethylation alone or in conjunction with histone-acetylation is not able to reconstitute the B-cell gene expression program in cultured HRS cells. Instead, combined DNA-demethylation and histone-acetylation of B cells induce a nearly complete extinction of their B-cell expression program and a tremendous up-regulation of numerous cHL characteristic genes including key players such as Id2 known to be involved in the suppression of the B-cell phenotype. Since the up-regulation of cHL characteristic genes and the extinction of the B-cell expression program occurred simultaneously, epigenetic changes may also be responsible for the malignant transformation of cHL. The epigenetic up-regulation of cHL characteristic genes thus play - in addition to promoter DNA-hypermethylation of B-cell associated genes a pivotal role for the reprogramming of HRS cells and explain why DNA-demethylation alone is unable to reconstitute the B-cell expression program in HRS cells.
Histone acetylation and DNA demethylation of B cells result in a Hodgkin-like phenotype.
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View SamplesIn this study we investigated to which extend aberrant c Myc activity plays a functional role in other aNHL and whether it is independent from MYC translocations. Based on a combined microarray analysis of human germinal centre (GC) B cells transfected with c Myc and 220 aNHLs cases, we developed a c Myc index.
High Myc activity is an independent negative prognostic factor for diffuse large B cell lymphomas.
Specimen part, Treatment
View SamplesTo characterize the molecular origin of primary lymphomas of the central nervous system (PCNSL), 21 PCNSL of immunocompetent patients were investigated by microarray-based gene expression profiling. Comparison of the transcriptional profile of PCNSL with various normal and neoplastic B cell subsets demonstrated PCNSL (i) to display gene expression patterns most closely related to late germinal center B cells, (ii) to display a gene expression profile similar to systemic diffuse large B cell lymphomas (DLBCL), and (iii) to be in part assigned to the activated B cell-like (ABC) or the germinal center B cell-like (GCB) subtype of DLBCL.
Gene expression profiling suggests primary central nervous system lymphomas to be derived from a late germinal center B cell.
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View SamplesMost epithelial ovarian cancers are thought to arise from different cells in the ovarian or fallopian tube epithelium. We hypothesized that these distinct cells-of-origin may play a role in determining ovarian tumor phenotype and also could inform the molecular classification of ovarian cancer. To test this hypothesis, we developed new methods to isolate and culture paired normal human ovarian (OV) and fallopian tube (FT) epithelial cells from multiple donors without cancer and identified a cell-of-origin gene expression signature that distinguished these cell types within the same patient. Application of the OV versus FT cell-of-origin gene signature to gene expression profiles of primary ovarian cancers permitted identification of distinct OV and FT-like subgroups among these cancers. Importantly, the normal FT-like tumor classification correlated with a significantly worse disease-free survival. This work describes a new experimental method for culture of normal human OV and FT epithelial cells from the same patient. These findings provide new evidence that cell-of-origin is an important source of ovarian tumor heterogeneity and the associated differences in tumor phenotype.
Gene expression signature of normal cell-of-origin predicts ovarian tumor outcomes.
Subject
View SamplesTranscriptome and translatome analyses of 6 and 24 hours imbibed seeds dormant and non-dormant seeds of NILDOG1-Cvi with and without addition of the transcription inhibitor Cordycepin. NILDOG1-Cvi is the Ler WT containing an introgression of the Cvi accession on chromosome 5, which includes the DOG1 gene (Bentsink et al., 2006).
Combined transcriptome and translatome analyses reveal a role for tryptophan-dependent auxin biosynthesis in the control of DOG1-dependent seed dormancy.
Specimen part, Treatment
View SamplesWe analysed the transcriptome of dormant and after-ripened imbibed seeds of different genotypes (Landsberg erecta and the different NILs) to identify dormancy and after-ripening genes that are absolutely required for these traits.
Differentially expressed genes during the imbibition of dormant and after-ripened seeds - a reverse genetics approach.
Specimen part
View SamplesWe analyzed the transcriptome of dormant and after-ripened imbibed seeds of the Arabidopsis accession Cape verde Islands.
Dormant and after-Ripened Arabidopsis thaliana Seeds are Distinguished by Early Transcriptional Differences in the Imbibed State.
Specimen part, Time
View SamplesWe have developed an in vitro system of cancer cell redirection that employs the 1:50 ratio of cancer cells to normal cells. Using our in vitro system of cancer cell redirection we investigated the genetic profiles of erbB2-overexpressing mammary tumor-derived cells as they undergo the redirection phenomenon.
RNA Expression Profiling Reveals Differentially Regulated Growth Factor and Receptor Expression in Redirected Cancer Cells.
Specimen part
View SamplesTranscriptome analyses on seeds developed in different parental conditions
Effects of Parental Temperature and Nitrate on Seed Performance are Reflected by Partly Overlapping Genetic and Metabolic Pathways.
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View SamplesThe tyrosine kinase receptors HER2 and HER3 play an important role in breast cancer. The HER2/HER3 heterodimer is a critical oncogenic unit associated with reduced relapse-free and decreased overall survival. We provide gene expression profile of the mammary epithelial cells MCF10A expressing HER2, HER3 or HER2/HER3 and grown in three-dimensional cultures for 15 days in the presence of heregulin, a known HER3-ligand that stabilizes and activates the HER2/HER3 heterodimer.
Co-expression of HER2 and HER3 receptor tyrosine kinases enhances invasion of breast cells via stimulation of interleukin-8 autocrine secretion.
Cell line
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