Prostate Cancer CGH in a single large family
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Jim Stankovich
PROVIDER: E-GEOD-2681 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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. 36 tumour samples were expression profiled in 2-colour hybridisations with Stratagene Universal Human Reference RNA in the reference channel. There were no replicates.
2014-08-30 | E-GEOD-60850 | biostudies-arrayexpress
Project description:Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal brain cancer that arises in the brainstem of children with no effective treatment and near 100% fatality. The failure of most therapies can be attributed to the delicate location of these tumors and choosing therapies based on assumptions that DIPGs are molecularly similar to adult disease. Recent studies have unraveled the unique genetic make-up of this brain cancer with nearly 80% harboring a K27M-H3.3 or K27M-H3.1 mutation. However, DIPGs are still thought of as one disease with limited understanding of the genetic drivers of these tumors. To understand what drives DIPGs we integrated whole-genome-sequencing with methylation, expression and copy-number profiling, discovering that DIPGs are three molecularly distinct subgroups (H3-K27M, Silent, MYCN) and uncovering a novel recurrent activating mutation in the activin receptor ACVR1, in 20% of DIPGs. Mutations in ACVR1 were constitutively activating, leading to SMAD phosphorylation and increased expression of downstream activin signaling targets ID1 and ID2. Our results highlight distinct molecular subgroups and novel therapeutic targets for this incurable pediatric cancer. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from snap frozen biopsy and autopsy brain tissue from DIPG patients. Copy number analysis on Affymetrix 6.0 SNP arrays was performed for 45 paediatric DIPG samples, 27 matched normal brain samples, and HapMap samples.
2014-03-31 | E-GEOD-50024 | biostudies-arrayexpress
Project description:Clinical isolates of the porcine pathogen Actinobacillus pleuropneumoniae often form adherent colonies on agar plates due to expression of an operon, pgaABCD, encoding a poly-N-acetylglucosamine (PGA) extracellular matrix. The adherent colony phenotype, which correlates with the ability to form a biofilm on the surface of polystyrene plates, is lost following serial passage in broth culture, and repeated passage of the non-adherent variants on solid media does not result in reversion to the adherent colony phenotype. In order to investigate the regulation of PGA expression and biofilm formation in A. pleuropneumoniae, we screened a bank of transposon mutants of the non-adherent serovar 1 strain, S4074T, and identified mutations in two genes, rseA and hns, which resulted in formation of the adherent colony phenotype. In other bacteria, including the Enterobacteriaceae, H-NS acts as a global gene regulator, and RseA is a negative regulator of the extracytoplasmic stress response sigma factor, ?E. Transcription profiling of A. pleuropneumoniae rseA and hns mutants revealed that both ?E and H-NS independently regulate expression of the pga operon. Transcription of the pga operon is initiated from a ?E promoter site in the absence of H-NS, and up-regulation of ?E is sufficient to displace H-NS, allowing transcription to proceed. In A. pleuropneumoniae, H-NS does not act as a global gene regulator, but rather specifically regulates biofilm formation via repression of the pga operon. Positive regulation of the pga operon by ?E indicates that biofilm formation in is part of the extracytoplasmic stress response in A. pleuropneumoniae.
2010-04-22 | E-MEXP-2461 | biostudies-arrayexpress
Project description:Changing antigenic structure such as capsule polysaccharide is a common strategy for bacterial pathogen to evade host immune system. In this regard, the recent emergence of an invasive W:2a:P1.7-2,4 ST-11 strain in New Zealand, which is an uncommon pathogenic serogroup, was investigated for its genetic origins. Molecular typing of 103 meningococcal isolates with similar serotyping characteristics was undertaken to determine genetic relationships. Results indicated that the W:2a:P1.7-2,4 strain had emerged via capsule switching from an existing group C strain (C:2a:P1.7 2,4). Neither of the upstream and downstream sites of recombination could be elucidate but sequence analysis demonstrated that at least 45 kb of DNA was involved in the recombination event. This included the entire capsule gene cluster. Genomic DNA isolated from serogroup C strains (n=4) and serogroup W strains (n=4) were compared using Pan-neisseria DNA microarray.
2009-06-03 | E-MEXP-1910 | biostudies-arrayexpress
Project description:We have carried out microarray-based comparative genomic hybridisation (arrayCGH) on 100 favourable histology Wilms tumour samples taken at immediate nephrectomy in order to identify changes in DNA copy number associated with clinical outcome. Tumour DNA was co-hybridised with normal female genomic DNA onto microarrays consisting of 4263 BAC clones with an approximate 1Mb spacing throughout the genome. Data was normalised and quality-filtered, an adapted weights smoothing algorithm fitted, and changes in DNA copy number assessed for each clone.
2006-05-11 | E-TABM-10 | biostudies-arrayexpress
Project description:Diffuse intrinsic pontine glioma (DIPG) is one of the most devastating of paediatric malignancies and one for which no effective therapy exists. A major contributor to the failure of therapeutic trials is the assumption that biologic properties of brainstem tumours in children are identical to cerebral high-grade gliomas of adults. A better understanding of the biology of DIPG itself is needed in order to develop agents targeted more specifically to these childrenâs disease. Here we address this lack of knowledge by performing the first high-resolution SNP-based DNA microarray analysis of a series of DIPGs. Eleven samples (nine post-mortem and two pre-treatment surgical samples), the largest series thus far examined, were hybridized to Affymetrix SNP arrays (250k or 6.0). The study was approved by the Research Ethics Board at our institution (Hospital for Sick Children, Toronto, Ontario, Canada). All Array findings were validated using quantitative-PCR, fluorescence in-situ hybridization, immunohistochemistry and/or microsatellite analysis. Analysis of DIPG copy number alterations showed recurrent changes distinct from those of paediatric supratentorial high-grade astrocytomas. 36% of DIPGs had gains in PDGFRA and all showed PDGF-R-α expression. Gains in PARP-1 were identified in 3 cases. Pathway analysis revealed genes with loss of heterozygosity were enriched for DNA repair pathways. Our data provides the first, comprehensive high-resolution genomic analysis of paediatric DIPG. Our findings of recurrent involvement of the PDGFR pathway as well as defects in DNA repair pathways coupled with gain of PARP-1 highlight two potential, biologically-based, therapeutic targets directed specifically at this devastating disease. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from snap frozen biopsy and autopsy brain tissue from DIPG patients. Copy number analysis of Affymetrix 250K and 6.0 SNP arrays was performed for 11 paediatric DIPG samples, 7 matched normal brain samples, and HapMap samples.
2010-06-16 | E-GEOD-18828 | biostudies-arrayexpress
Project description:This study aimed to generate a new panel of comprehensively, genomically characterized high-grade serous ovarian carcinoma (HGSOC) cell line and xenograft models. Multidimensional genomic data were generated and compared between cell lines/xenografts and the tumours they were derived from, indicating the cell lines/xenografts are highly similar to their patient-matched tumours. Cell line/xenograft data were also compared to TCGA ovarian tumours to show the cell lines are good models of clinical HGSOC. Affymetrix SNP 6 arrays were performed according to the manufacturer's instructions on genomic DNA extracted from i) tumour cells purified from ovarian tumour ascites, ii) established cell lines, iii) patient derived xenografts, and iv) lymphoblast lines. Evaluation of the similarity in copy number/methylation/gene expression/mutational profiles of cell lines/tumours/xenografts was performed.
2016-08-11 | E-GEOD-71522 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-08-30 | E-GEOD-60940 | biostudies-arrayexpress
Project description:Obesity is characterized by a chronic auto-inflammation of the hypertrophied white adipose tissue (WAT) associated with metabolic and vascular complications. WAT of obese subjects produces inflammatory factors like cytokines (IL6, TNF-alpha) and chemokines (CCL2 and IL-8) originating mainly from the accumulated macrophages. WAT macrophages profoundly affect adipose cell biology leading in particular to the inflammation of the adipocytes and altered differentiation of their precursors, the pre-adipocytes. We previously showed that conditioned media from WAT macrophages (ATM CM) induced inflammation in human pre-adipocytes. We performed pangenomic cDNA microarrays analysis to compare gene expression profiles between control and ATM CM treated preadipocytes. By a functional analysis, we identified the biological themes that best characterized the proinflammatory preadipocytes. The most significantly overrepresented GO Cellular Component categories were "cytokine-cytokine receptor interaction" and "chemokine signaling pathway", emphasizing the importance of cytokine and chemokine production by the inflammatory preadipocyte. The chemokines acting in concert to recruit leukocytes in inflamed tissues, still need to be more precisely identified in human WAT. Thus, our data lead to the identification of new chemokines involved in attraction of immune cells in inflamed human WAT. The transcriptomic profile of human preadipocytes was compared to that of preadipocyes treated by macrophages isolated from human adipose tissue. Two-condition experiment,human control preadipocyte vs preadipocyte treated by macrophages from adipose tissue. 5 biological replicates (with a dye-swap design).
2013-03-22 | E-GEOD-28445 | biostudies-arrayexpress
Project description:Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in Western countries. The main genetic alterations associated to this disease are loss of 13q14, loss of 11q23, trisomy 12 and, less frequently, 17p13 losses, and are routinely studied using fluorescence in situ hybridization. These genomic aberrations have been demonstrated to be important independent predictors of disease progression in CLL and their detection currently has a direct implication in the treatment strategy of the patients. It has been widely demonstrated that array-based karyotyping clearly detects DNA gains and losses and allows the identification of CLL abnormalities not included in the standard FISH panel. We have here established and tested an oligonucleotide-based array platform for the diagnosis of CLL that interrogates the most relevant chromosomal regions related with the disease and may help in the differential diagnosis between CLL and other small B-cell leukemias and may be used as a powerful prognosis tool to stratify the CLL patients. Copy number analysis using Custom Agilent 60K was performed on 47 chronic lymphocytic Leukemia patients with sex-matched control DNAs
2015-08-31 | E-GEOD-66922 | biostudies-arrayexpress