Genetic and epigenetic processes result in gene expression changes through alteration of the chromatin structure. The relative position of genes on chromosomes has therefore important functional implications and can be exploited to model microarray datasets. Gliomas are the most frequent primary brain tumours in adults and their prognosis is related to histology and grade. In oligodendrogliomas, allelic loss of 1p/19q and hypermethylation of MGMT promoter is associated with longer survival and chemosensitivity. In this work we used oligonucleotide microarray to study a group of 30 gliomas with various oligodendroglial and astrocytic components. We used an original approach combining a wavelet model of inter-probe genomic distance (CHROMOWAVE) and unsupervised method of analysis (Singular Value Decomposition) in order to discover new prognostic chromosomal patterns of gene expression. We identified a major pattern of variation that strongly correlated with survival (p= 0.007) and could be visualized as a genome-wide chromosomal pattern including widespread gene expression changes on 1p, 19q, 4, 18, 13 and 9q and multiple smaller clusters scattered along chromosomes. Gene expression changes on chromosomes 1p, 19q and 9q were significantly correlated with the allelic loss of these regions as measured by FISH. Differential expression of genes implicated in drug resistance was also a feature of this chromosomal pattern and in particular low expression of MGMT was correlated with favourable prognosis (p<0.0001). Remarkably, unsupervised analysis of the expression of individual genes and not of their chromosomal ensemble produced a pattern that could not be associated with prognosis, emphasizing the determinant role of the wavelet mathematical modelling.
Chromosomal patterns of gene expression from microarray data: methodology, validation and clinical relevance in gliomas.
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View SamplesThe initiation of the mucosal immune response in Peyers patch (PP) relies on the sampling, processing and efficient presentation of foreign antigens by dendritic cells (DC). PP DC encompass five subsets, among which CD11b+ conventional DC (cDC) and LysoDC have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here, we have studied the genetic relatedness of the different subsets of PP cDC at steady state and under TLR7 ligand stimulation. We also provide the transcriptional profiles of subepithelial TIM-4- and interfollicular TIM-4+ macrophages.
Distribution, location, and transcriptional profile of Peyer's patch conventional DC subsets at steady state and under TLR7 ligand stimulation.
Sex, Age, Specimen part, Treatment
View SamplesParkinsons Disease is a multi-system, disabling progressive neurodegenerative condition. Clinical progression is highly heterogeneous and, thus far, there are not available biomarkers to accurately predict the rate of disease progression. Thus, identifying molecular signatures that allow discriminating between different progression rates might significantly assist the therapeutic strategy, and enable improved outcomes in clinical trials.
Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles.
Sex, Specimen part
View SamplesSpinocerebellar ataxia type 3 (SCA3) is one of the polyglutamine (polyQ) diseases, which are caused by a CAG repeat expansion within the coding region of the associated genes.
Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila.
Sex, Specimen part
View SamplesThis study aimed to identify genes that are linked with optineurin expression using a combined siRNA-microarray approach
Identification of genes that are linked with optineurin expression using a combined RNAi--microarray approach.
No sample metadata fields
View SamplesBackground: Glioblastoma multiforme (GBM) is the most aggressive and most lethal primary malignant brain tumor, correlated with survival rates of less than one year from the time of diagnosis. Current surgical procedure attempts to remove the bulk of the tumor mass, whereas GBM frequently recurs within 1-3cm from the primary tumor resection site. Molecular mechanisms involved in the recurrence of the tumor are still poorly understood. The aim of the study was to define the molecular signature of GBM surrounding white matter (WM) in order to better understand the molecular mechanisms involved with tumor relapse.
Gene expression profile of glioblastoma peritumoral tissue: an ex vivo study.
No sample metadata fields
View SamplesThe pre-synaptic protein -synuclein is a key player in the pathogenesis of Parkinson's disease. Together with accumulation and missfolding of -synuclein protofibrils serve as seed structures for the aggregation of numerous proteins in the cytoplasm of neuronal cells, the so-called Lewy bodies. Furthermore, missense mutations in the SNCA gene and gene multiplications lead to autosomal dominant forms of familiar PD. However, so far the exact biological role of -synuclein in normal brain is elusive. To gain more insights into the biological function of this protein we monitored whole genome expression changes in dopaminergic neuroblastoma cells (SH-SY5Y) caused by a 90% reduction of -synuclein by RNA interference.
Microarray expression analysis of human dopaminergic neuroblastoma cells after RNA interference of SNCA--a key player in the pathogenesis of Parkinson's disease.
No sample metadata fields
View SamplesIn an effort to identify genes whose expression is regulated by activated PI3K signaling, we performed microarray analysis and subsequent qRT-PCR on an isogenic set of PTEN gene-targeted human cancer cells. Numerous p53 effectors were upregulated following PTEN deletion, including p21, GDF15, PIG3, NOXA, and PLK2. Stable depletion of p53 led to reversion of the gene expression program. Western blots revealed that p53 was stabilized in HCT116 PTEN-/- cells via an Akt1-dependent and p14ARF-independent mechanism. Stable depletion of PTEN in untransformed human fibroblasts and epithelial cells also led to upregulation of p53 and senescent-like growth arrest. Simultaneous depletion of p53 rescued this phenotype, enabling PTEN-depleted cells to continue proliferating. Next, we tested whether oncogenic PIK3CA, like inactivated PTEN, could activate p53. Retroviral expression of oncogenic human PIK3CA in MCF10A cells led to activation of p53 and upregulation of p53-regulated genes. Stable depletion of p53 reversed these PIK3CA-induced expression changes and synergized with oncogenic PIK3CA in inducing anchorage-independent growth. Finally, targeted deletion of an endogenous allele of oncogenic but not wild-type PIK3CA in a human cancer cell line led to a reduction in p53 levels and a decrease in the expression of p53-regulated genes. These studies demonstrate that activation of PI3K signaling by mutations in PTEN or PIK3CA can lead to activation of p53-mediated growth suppression in human cells, indicating that p53 can function as a brake on PIP3-induced mitogenesis during human cancer pathogenesis.
Activation of p53-dependent growth suppression in human cells by mutations in PTEN or PIK3CA.
No sample metadata fields
View SamplesThe identification of the most appropriate T-cell subset to ensure optimal persistence and anti-tumor activity is a major goal of cancer immunotherapy. We identified a novel post-mitotic CD45RA+CD62L+ T cell subpopulation (TTN), generated in vitro upon activation of nave T (TN) cells with beads conjugated to anti-CD3 and anti-CD28 antibodies. This cell population is highly proliferative, produces low levels of IFNg and cytotoxic molecules, and requires IL-7 and IL-15 for in vitro expansion.
IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors.
No sample metadata fields
View SamplesThere is a controversy surrounding the existence of palmoplantar pustulosis (PPP) and palmoplantar pustular psoriasis (PPPP) as separate clinical entities or as variants of the same clinical entity. We used gene expression microarray to compare gene expression in PPP and PPPP. PPP and PPPP could not be differentiated using gene expression microarray suggesting that they are not distinct clinical entities. Increased expression of GPRIN1, and ADAM23 in keratinocytes suggests that these proteins could be new therapeutic targets for PPP/PPPP.
Based on Molecular Profiling of Gene Expression, Palmoplantar Pustulosis and Palmoplantar Pustular Psoriasis Are Highly Related Diseases that Appear to Be Distinct from Psoriasis Vulgaris.
Specimen part, Disease, Subject
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