Genome-wide analysis of hemangiosarcoma tumor tissue using ChRO-seq finds ECM remodeling plays an important role in canine hemangiosarcoma pathogenesis.
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PROVIDER: PRJNA633277 | ENA |
REPOSITORIES: ENA
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Project description:Canine hemangiosarcoma (HSA) is an aggressive vascular tumor that arise from malignant endothelial cells. To gain deeper understanding of HSA pathogenesis, we performed Chromatin-Run-On sequencing (ChRO-seq) experiment on 17 HSA tumor tissues and 4 normal tissue. ChRO-seq analysis revealed over a thousand differentially expressed genes in HSA tissue compared with normal splenic tissue (FDR <0.005). Interestingly the majority of genes overexpressed in HSA tumor tissue were associated with extracellular matrix (ECM) remodeling. This observation correlated well with our histological analysis, which found that HSA tumors contain a rich and complex collagen network. Additionally, we characterized the protein expression patterns of two highly overexpressed molecules identified in ChRO-seq analysis, podoplanin (PDPN) and laminin alpha 4 (LAMA4). We found that the expression of these two ECM-associated factors appeared to be largely limited to transformed endothelial cells within the HSA lesions. Outcomes from this study suggest that ECM remodeling has an important role in HSA pathogenesis.
2020-05-19 | GSE150705 | GEO
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| S-EPMC7310061 | biostudies-literature
Project description:Cell lines and tumor tissues from canine hemangiosarcoma derived cell lines and hemangiosarcoma tissue samples
2014-12-08 | GSE46040 | GEO
Project description:Cell lines and tumor tissues from canine hemangiosarcoma derived cell lines and hemangiosarcoma tissue samples Identification of three molecular and functional subtypes in canine hemangiosarcoma through gene expression profiling
2014-12-11 | E-GEOD-53219 | biostudies-arrayexpress
Project description:Cell lines and tumor tissues from canine hemangiosarcoma derived cell lines and hemangiosarcoma tissue samples
2014-12-11 | GSE53219 | GEO
Project description:The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease. We first evaluated mutational events in candidate genes that might drive hemangiosarcoma. Each of 10 tumor and four non-tumor samples had wild type sequence for these genes. Thus, we used gene expression profiling as a global approach to test the hypothesis. Hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on robust signatures that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. The data do not distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that the cells that give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. Keywords: Hemangiosarcoma, microarray, heritability, GSEA, canine 10 dogs with hemangiosarcoma were compared to 3 dogs without hemangiosarcoma and 21 dogs with other tumors
2010-06-16 | E-GEOD-22129 | biostudies-arrayexpress
Project description:The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease. We first evaluated mutational events in candidate genes that might drive hemangiosarcoma. Each of 10 tumor and four non-tumor samples had wild type sequence for these genes. Thus, we used gene expression profiling as a global approach to test the hypothesis. Hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on robust signatures that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. The data do not distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that the cells that give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. Keywords: Hemangiosarcoma, microarray, heritability, GSEA, canine
2010-06-04 | GSE22129 | GEO
Project description:Abnormal function of genes is at the root of most cancers, but heritable cancer syndromes account for a very small minority of all tumors in humans and domestic animals. The majority of cancers are “sporadic,” that is, they are not heritable in the strictest sense. Instead, sporadic cancers occur due to interactions of unknown intrinsic (heritable) and environmental factors that lead to malignant transformation and uncontrolled growth. Identification of heritable risk factors in sporadic human cancers is difficult because individual genetic backgrounds are very heterogeneous. To this end, individual genetic backgrounds of purebred dogs are more homogeneous, and dog breeds show different predilection to develop specific cancers. Here, we used genomic screens based on gene expression profiling to identify sets of genes that may contribute to the development of canine hemangiosarcoma, a relatively common endothelial sarcoma. Specific genes in a single breed (Golden Retrievers) are modulated by (or with) heritable risk traits, showing functional features that appear to modulate tumor behavior. Our results suggest these methods are suitable to identify genes that will enhance our understanding of how these cancers happen, as well as possible treatment targets that will improve outcomes of both human and canine cancer patients. Keywords: Hemangiosarcoma, microarray, heritability, GSEA, canine 10 samples were analysed. 6 Golden Retrievers with hemangiosarcoma, 3 non-Golden Retrievers with hemangiosarcoma, and 1 mixed breed Golden Retriever with hemangiosarcoma. The experiment was designed to find genes associated with breed and hemangiosarcoma to asses genetic make-up on disease susceptibility and/or progression
2009-03-06 | E-GEOD-15086 | biostudies-arrayexpress
Project description:Purpose: In recent years, the mutation of ZNF469 is considered to be one of the pathogenesis of brittle cornea syndrome（BCS）. We establish a znf469 mutant zebrafish line to explore its phenotype and the possible molecular mechanism. Methods: We generated the znf469 mutant zebrafish by using the CRISPR/Cas9 system. TEM is applied to examine the phenotype of the cornea in different development stage. RNA sequencing and quantitative RT-PCR are used to reveal the molecular mechanism. Results: Macroscopically, the homozygous znf469-4del zebrafish larva exhibited a curved body from 72 hpf similar to kyphoscoliosis and a noninflated swimbladder at 7 dpf. TEM reveals the extreme reduction of corneal stroma in homozygous znf469-4del zebrafish in both central and peripheral cornea since the early development stage. RNA-seq analysis demonstrates that the znf469 mutation leads to the decreased synthesis of various ECM component like collagens and proteoglycans but increased synthesis of 26S proteasome families. Conclusion: Our work indicates that znf469 is a critical gene that encoding a transcription factor, regulating the synthesis and degradation of a large number of ECM components which is also the pathologic basis of the ocular and extraocular phenotypes in the znf469 mutant zebrafish model.
2023-03-24 | GSE225418 | GEO
Project description:Background The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease. Methods We first investigated mutations of VHL and Ras family genes that might drive hemangiosarcoma by sequencing tumor DNA and mRNA (cDNA). Protein expression was examined using immunoblotting. Next, we evaluated genome-wide gene expression profiling using the Affymetrix Canine 2.0 platform as a global approach to test the hypothesis. Data were evaluated using routine bioinformatics and validation was done using quantitative real time RT-PCR. Results Each of 10 tumor and four non-tumor samples analyzed had wild type sequences for these genes. At the genome wide level, hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on a robust signature that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. This signature did not simply reflect a cancer-associated angiogenic phenotype, as it also distinguished hemangiosarcoma from non-endothelial, moderately to highly angiogenic bone marrow-derived tumors (lymphoma, leukemia, osteosarcoma). Conclusions The data show that inflammation and angiogenesis are important processes in the pathogenesis of vascular tumors, but a definitive ontogeny of the cells that give rise to these tumors remains to be established. The data do not yet distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that cells which give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. We propose that the frequent occurrence of canine hemangiosarcoma in defined dog breeds, as well as its similarity to homologous tumors in humans, offers unique models to solve the dilemma of stem cell plasticity and whether angiogenic endothelial cells and hematopoietic cells originate from a single cell or from distinct progenitor cells. This SuperSeries is composed of the SubSeries listed below.
2010-08-24 | GSE23760 | GEO