Genomic copy number changes in breast cancers from patients exposed to ioinising radiation and non-exposed controls.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Kristian Unger
PROVIDER: E-MTAB-6176 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Purpose: Preclinical model systems should faithfully reflect the complexity of the human pathology. In hepatocellular carcinoma (HCC), the tumor vasculature is of particular interest in diagnosis and therapy. By comparing two commonly applied preclinical model systems, diethylnitrosamine induced (DEN) and orthotopically implanted (McA) rat HCC, we aimed to measure tumor biology non-invasively and identify differences between the models.<br>Experimental design: DEN and McA tumor development was monitored by magnetic resonance imaging (MRI) and positron emission tomography (PET). A slice-based correlation of imaging and histopathology was performed. Array CGH analyses were applied to determine genetic heterogeneity. Therapy response to sorafenib was tested in DEN and McA tumors.<br>Results: Histologically and biochemically confirmed liver damage resulted in increased 18F-fluordeoxyglucose (FDG) PET uptake and perfusion in DEN animals only. DEN tumors exhibited G1-3 grading compared to uniform G3 grading of McA tumors. Array comparative genomic hybridization revealed a highly variable chromosomal aberration pattern in DEN tumors. Heterogeneity of DEN tumors was reflected in more variable imaging parameter values. DEN tumors exhibited lower mean growth rates and FDG uptake and higher diffusion and perfusion values compared to McA tumors. To test the significance of these differences, the multikinase inhibitor sorafenib was administered, resulting in reduced volume growth kinetics and perfusion in the DEN group only.<br>Conclusion: This work depicts the feasibility and importance of in depth preclinical tumor model characterization and suggests the DEN model as a promising model system of multifocal nodular HCC in future therapy studies.
2016-03-25 | E-MTAB-3507 | biostudies-arrayexpress
Project description:162 FFPE samples, representing six different tumour types, were profiled in triplicate across three independent laboratories. OncoScan¬ FFPE assay data was then analysed for reproducibility of genome-wide copy number, loss of heterozygosity and somatic mutations.
2015-02-18 | E-MTAB-2914 | biostudies-arrayexpress
Project description:Background Renal oncocytomas (ROs) are benign epithelial tumors of the kidney that may progress into malignant chromophobe renal cell carcinoma (chRCCs), with the latter constituting 5 – 7 % of renal neoplasias. ROs and chRCCs show pronounced molecular and histological similarities, which renders their differentiation demanding. We aimed for the differential proteome profiling of ROs and chRCCs in order to better understand distinguishing protein patterns. Methods We employed formalin-fixed, paraffin-embedded samples (six RO cases, six chRCC cases) together with isotopic triplex dimethylation and a pooled reference standard to enable cohort-wide quantitative comparison. For lysosomal-associated membrane protein 1 (LAMP1) and integrin alpha-V (ITGAV) we performed corroborative immunohistochemistry (IHC) in an extended cohort of 42 RO cases and 31 chRCC cases lacking any overlap with the smaller proteomic cohort. Results: At 1 % false discovery rate, we identified > 3900 proteins, of which >2400 proteins were consistently quantified in at least four RO and four chRCC cases. The proteomic expression profiling discriminated ROs and chRCCs and highlighted established features such as accumulation of mitochondrial proteins in ROs together with emphasizing the accumulation of endo-lysosomal proteins in chRCCs. In line with the proteomic data, IHC showed enrichment of LAMP1 in chRCC and of ITGAV in RO. Conclusion We present one of the first differential proteome profiling studies on ROs and chRCCs and highlight differential abundance of LAMP1 and ITGAV in these renal tumors.
2018-08-13 | PXD009300 | Pride
Project description:Illumina Infinium MethylationEPIC BeadChip array files from phaeochromocytoma, paraganglioma tumours of different genotypes and normal adrenal medulla control samples. This is the first study using high-resolution MethylationEPIC arrays and also includes a large number of Cluster 1 tumours (n=16) which exhibit extensive epigenetic deregulation.
2023-12-21 | E-MTAB-13433 | biostudies-arrayexpress
Project description:Stratification of a retrospective cohort of HGSOC based on its tissues of origin.
2020-09-29 | E-MTAB-9605 | biostudies-arrayexpress
Project description:Soft tissue sarcomas (STS) often present a significant diagnostic challenge as many STS bear histologic resemblance, but are known to have very different clinical and biologic characteristics. Some STS subtypes are characterized by specific genetic abnormalities and this has helped in their classification, diagnosis and even treatment. However, a large majority of STS have no known specific genetic aberrations even though they almost always have highly aberrant karyotypes. We therefore hypothesize that the latter subgroup of STS bear genetic abnormalities that are sub-type specific, but as yet unidentified. High-resolution mapping of copy number aberrations in cancer genomes is a valuable way of identifying recurrent genomic changes that could be of pathogenetic significance. Traditionally, this has been done using high quality DNA obtained from fresh frozen tissue or cells and archived tissue is generally regarded as unsuitable because of the degradative effects of formalin fixation on DNA. Utility of archival tumour material for such molecular genetic analysis is vital, especially for rare cancers like STS but recent efforts to accomplish this have produced variable results. We therefore set out, in addition to optimize a protocol for obtaining genomic copy number data from formalin-fixed, paraffin-embedded (FFPE) STS material that is comparable to that from fresh frozen (FF) material. Microarray-based Comparative Genomic Hybridization (aCGH), a high- resolution, genome-wide method was used to identify somatic copy number aberrations (SCNAs) in primary STS samples (fresh frozen and archival FFPE), using an optimized protocol for labeling DNA. Findings were confirmed using Conventional Cytogenetics and Fluorescence in-situ Hybridization (FISH). Data obtained from paired samples (FF and FFPE) of the same tumours showed similar results and array results were consistently of good quality. On-going analysis of the recurrent SCNAs in combination with expression data and clinical correlates may serve to identify specific patterns that can serve as diagnostic markers, characterize subgroups with prognostic implication or identify potential therapeutic targets. To identify common CNAs among LMS fresh and FFPE. 25 samples in total: 22 individual FFPE cases; 3 cases also obtained fresh. Reference DNA was obtained from same patient when possible, otherwise commercial genomic DNA was used [Promega® UK with Cat Nos. G1471 (male) and G1521 (female)].
2015-07-24 | E-GEOD-39663 | biostudies-arrayexpress
Project description:Objectives: The primary objective of this high-resolution proteomic study was to investigate patients with severe aortic valve stenosis (AVS) to detect novel biomarkers for diagnostic and/or therapeutic purposes. Background: Among patients with severe AVS, some are likely to rapidly progress with a higher mortality and benefit from prompt surgical or interventional care. To select these patients, novel disease-related biomarkers are needed. Methods: We used induced pluripotent stem cell derived cardiomyocytes as a relative quantification standard to profile the proteomes of formalin-fixed paraffin-embedded (FFPE) atria and left ventricles from 30 patients with AVS. Results: In total, 3370 proteins were quantified using high-resolution mass spectrometry. Statistical analysis revealed significant upregulation of 64 proteins in the atria and 27 proteins in the ventricles including several known chamber specific marker-proteins. Atrial upregulation of proteins that belong to the interstitial compartment or contribute to endocrine function was observed. To uncover disease related proteins, we compared our data to similar published datasets from healthy and diseased hearts. We performed gene set enrichment analyses to pinpoint global proteomic characteristics of a decompensated state of AVS with hypertrophy, like the downregulation of ventricular mitochondrial proteins and the development of ventricular fibrosis. Finally, we propose a set of high abundant proteins like LGALS3BP, TUBA4A, TINAGL1 and LAMA2 as well as SRL, FHL1 and ATP2A2 playing a crucial role in AVS-related heart disease. Conclusions: We established a reproducible workflow for high-resolution quantitative proteomics of FFPE myocardial samples and provide interesting candidate proteins with biomarker potential for AVS.
2023-01-09 | PXD014297 | Pride
Project description:Pathology archives contain vast resources of clinical material in the form of formalin-fixed paraffin embedded (FFPE) tissue samples. Due to the methods of tissue fixation and storage, the integrity of DNA and RNA available from FFPE tissue is compromised, meaning obtaining informative data regarding epigenetic, genomic and expression alterations can be challenging. Here we have investigated the utility of repairing damaged DNA derived from FFPE tumours prior to single nucleotide polymorphism (SNP) arrays for whole genome DNA copy number analysis. To investigate whether repairing the DNA might improve performance in SNP array assay, we used the DNA Restore protocol from Illumina as a pre-treatment step prior to applying the DNA to the Infinium assay using the Human CytoSNP FFPE-12v2.1 arrays. DNA was extracted from FFPE samples spanning five decades involving tumor material obtained from surgical specimens and post-mortems. Various aspects of the protocol were assessed, including the method of DNA extraction, the role of Quality Control quantitative PCR in predicting sample success and the effect of DNA restoration on assay performance, data quality and the prediction of copy number aberrations (CNAs). In total 8 cases were analysed in this experiment, involving 43 SNP arrays of tumour and matched normal DNA samples, replicates and other control arrays.
2013-07-01 | E-GEOD-43406 | biostudies-arrayexpress
Project description:Comparison of the genomic copy number status of livers from wildtype mice (reference) with Tak1/Casp8 knockout mice or Tak1/LPC knockout mice or Tak1/LPC/RIP3 knockout mice.
2013-07-22 | E-MTAB-1559 | biostudies-arrayexpress
Project description:Genomic copy number profiling of hepatocellular carcinomas (HCC) from IKKβ(EE)Hep mice (C57BL/6) constitutively expressing IKKβ in the liver without and after treatment with DEN (diethylnitrosamine) and of HCCs that developed in wild type mice (C57BL/6) after DEN treatment.
2015-09-25 | E-MTAB-3848 | biostudies-arrayexpress