Among B-cell lymphomas mantle cell lymphoma (MCL) has the worst prognosis. By using a combination of genomic and expression profiling (Affymetrix GeneChip Mapping 10k Xba131 and U133 set), we analysed 26 MCL samples to identify genes relevant to MCL pathogenesis and that could represent new therapeutic targets. Recurrent genomic deletions and gains were detected. Genes were identified as overexpressed in regions of DNA gain on 3q, 6p, 8q, 9q, 16p and 18q, including the cancer genes BCL2 and MYC. Among the transcripts with high correlation between DNA and RNA, we identified SYK, a tyrosine kinase involved in B-cell receptor signalling. SYK was amplified at DNA level, as validated by fluorescence in situ hybridisation (FISH) analysis, and overexpressed at both RNA and protein levels in the JeKo-1 cell line. Low-level amplification, with protein overexpression of Syk was demonstrated by FISH in a small subset of clinical samples. After treatment with low doses of the Syk inhibitor piceatannol, cell proliferation arrest and apoptosis were induced in the cell line overexpressing Syk, while cells expressing low levels of Syk were much less sensitive. A combination of genomic and expression profiling suggested Syk inhibition as a new therapeutic strategy to be explored in lymphomas.
Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma.
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View SamplesWe compared gene and protein expression profiles in cells challenged with ER stress-inducing drugs or expressing model polypeptides. Drugs titration to limit up-regulation of the endogenous ER stress reporters BiP/HSPA5 and HERP/HERPUD1 to levels comparable to luminal accumulation of unfolded proteins substantially reduced the amplitude of transcriptional and translational responses.
No associated publication
Cell line, Treatment
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Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression.
Sex, Age, Specimen part, Race, Subject
View SamplesCongenital malformations in facial bones significantly impact the overall representation of the face. Establishing correlations between gene expression and morphogenesis of craniofacial structures may lead to new discoveries of molecular mechanisms of craniofacial development. Thus in the present investigation, we will generate gene expression profiles of facial bones at embryo stage 14.5 to establish their roles in regulating craniofacial development.
No associated publication
Specimen part
View SamplesGene expression profiling of 60 lung adenocarcinoma tumors and their matched histologically normal adjacent lung tissue samples were analyzed using Illumina HumanWG-6 v3.0 expression beadchip. We integrated these data with DNA methylation profiles of the same samples to identify potential DNA methylation regulated genes.
Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression.
Sex, Age, Specimen part, Race, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Induced pluripotent stem cell models of Zellweger spectrum disorder show impaired peroxisome assembly and cell type-specific lipid abnormalities.
Specimen part
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Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor Guadecitabine (SGI-110) in Hepatocellular Carcinoma.
Cell line, Treatment, Time
View SamplesCongenital malformations in facial bones significantly impact the overall representation of face. Establishing a correlations between gene expression and morphogenesis of craniofacial structures may lead to new discoveries of molecular mechanisms of craniofacial development. Thus in the present investiation we will generate gene expression profile of different facial bones at different time intrevals over a period of 5 years to establish their roles in regulating craniofacial development
No associated publication
Specimen part
View SamplesAcute kidney injury (AKI) is associated with an abrupt loss of kidney function that results in significant morbidity and mortality. Considerable effort has focused around the identification of diagnostic biomarkers and the analysis of molecular events. Most studies have adopted organ-wide approaches that do not fully capture the interplay among different cell types in the pathophysiology of AKI. To extend our understanding of molecular and cellular events in AKI, we developed a mouse line that enables the identification of translational profiles in specific cell types by CRE recombinase-dependent activation of an eGFP-tagged L10a ribosomal protein subunit, and consequently, translating ribosome affinity purification (TRAP) of mRNA populations. By utilizing cell-type specific CRE-driver lines, in this study we identify distinct cellular responses in an ischemia reperfusion injury (IRI) model of AKI. Cell-specific translational expression profiles were uncovered 24 hours after IRI from four populations enriched for distinct anatomical and cellular subgroups: nephron, interstitial cell populations, vascular endothelium, and macrophages/monocytes by Affymetrix microarray.
Cell-specific translational profiling in acute kidney injury.
Sex, Age, Specimen part, Treatment
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Genome-wide profiling identifies a DNA methylation signature that associates with TET2 mutations in diffuse large B-cell lymphoma.
Specimen part
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