Resolution of genome-wide molecular signals in canine mammary tumor model
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ABSTRACT:
ORGANISM(S): Canis lupus familiaris
PROVIDER: GSE136197 | GEO | 2020/12/14
REPOSITORIES: GEO
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Project description:Molecular mechanisms of the canine mammary malignancy. RNA isolated from canine mammary tumours of the 3rd grade of malignancy was pooled and hybrydized on the same microarray as RNA isolated from canine mammary tumours of the 1st grade of malignancy. Based on the results the "malignancy portrait" was assessed.
2013-10-01 | GSE44033 | GEO
Project description:Molecular mechanisms of the canine mammary malignancy. RNA isolated from canine mammary tumours of the 3rd grade of malignancy was pooled and hybrydized on the same microarray as RNA isolated from canine mammary tumours of the 1st grade of malignancy. Based on the results the "malignancy portrait" was assessed. Dye-swap experiment, gene expression in the most malignant canine mammary tumours (the 3rd grade of malignancy) was compared to the less malignant tumours (1st grade of malignancy).
2013-10-01 | E-GEOD-44033 | biostudies-arrayexpress
Project description:Spontaneously occurring canine mammary cancer (MC) represents an excellent model of human breast cancer, but is greatly understudied. We performed high density arrays on 12 canine MC cases, including 7 simple carcinomas and four complex carcinomas. Simple carcinomas, which histologically match human breast carcinomas, harbor extensive genomic aberrations, many faithfully recapitulating key features of human breast cancer. Complex carcinomas, with luminal and myoepithelial cells both proliferating (which is rare in human breast cancer), appear to lack genomic abnormalities. Comparison of CNAs from canine mammary simple carcinomas and complex carcinomas
2014-09-07 | E-GEOD-54535 | biostudies-arrayexpress
Project description:The objective of the present study was to assess the gene expression profiles of canine mammary carcinoma (in unsupervised manner) classified by pathologists as the 1st, the 2nd and the 3rd grade of malignancy and compare their molecular and pathological classifications. Our analysis showed that some pathologically distinct tumours may have similar gene expression and vice-versa. Probably that is why the patients with the same pathological type of cancer often have various outcomes and respond in a heterogenous manner to anticancer agents. The molecular classification, contrary to the pathological methods, reflects the biological processes and pathways within the tumour cell, not only the morphological features. It is also helpful in the better understanding of cancer biology (genes responsible for tumourigenesis, molecular interactions within the tumour or genes involved in specific pathways which could be a target for future therapy). 18 canine mammary tumours (6 of the 1st grade of malignancy, 6 of the 2nd grade of malignancy and 6 of the 3rd grade of malignancy) were subjected to the analysis. RNA was isolated, reverse transcribed and hybridized on cDNA microarrays. Pooled RNA from all of the tumours was used as a reference, and dye-swaps were performed. Then, the unsupervised hierarchical analysis was performed.
2013-05-31 | E-GEOD-43778 | biostudies-arrayexpress
Project description:Resolution of genome-wide molecular signals in canine mammary tumor model
| PRJNA561580 | ENA
Project description:Cancer stem cells (CSCs) are fundamental to bladder cancer progression and the cyclooxygenase-2 (COX-2) pathway has a pro-tumorigenic role in CSC function. Naturally occurring bladder cancer in dogs has the potential to be a natural model of the human disease. Here, we used canine specific microarrays to determine changes in global gene expression of canine bladder cancer cells (the K9TCC cell line) and bladder cancer stem cells isolated from the K9TCC cell line after treatment with the selective COX-2 inhibitor mavacoxib or a COX-2 siRNA.
2022-07-20 | GSE183793 | GEO
Project description:Spontaneously occurring canine mammary cancer represents an excellent model of human breast cancer, but is greatly understudied. To better use this valuable resource, we performed whole-genome sequencing, whole-exome sequencing, RNA-seq, and/or high-density arrays on twelve canine mammary cancer cases, including seven simple carcinomas and four complex carcinomas. Canine simple carcinomas, which histologically match human breast carcinomas, harbor extensive genomic aberrations, many of which faithfully recapitulate key features of human breast cancer. Canine complex carcinomas, which are characterized by proliferation of both luminal and myoepithelial cells and are rare in human breast cancer, seem to lack genomic abnormalities. Instead, these tumors have about 35 chromatin-modification genes downregulated and are abnormally enriched with active histone modification H4-acetylation, whereas aberrantly depleted with repressive histone modification H3K9me3. Our findings indicate the likelihood that canine simple carcinomas arise from genomic aberrations, whereas complex carcinomas originate from epigenomic alterations, reinforcing their unique value. Canine complex carcinomas offer an ideal system to study myoepithelial cells, the second major cell lineage of the mammary gland. Canine simple carcinomas, which faithfully represent human breast carcinomas at the molecular level, provide indispensable models for basic and translational breast cancer research.
2014-09-07 | GSE54535 | GEO
Project description:[original title] Metastatic Canine Mammary Carcinomas can be Identified by a Gene Expression Profile that partly Overlaps with Human Breast Cancer Profiles. Introduction: Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods: Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results: Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions: Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets.
2010-12-01 | GSE20718 | GEO
Project description:[original title] Metastatic Canine Mammary Carcinomas can be Identified by a Gene Expression Profile that partly Overlaps with Human Breast Cancer Profiles. Introduction: Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods: Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results: Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions: Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets. Thirteen simple mammary carcinomas with invasive growth and lymph node metastases at the time of tumor resection and 14 simple carcinomas without lymph node metastases were included in the study. None of the patients had radiographically detectable pulmonary metastases at the time of tumor resection. Distant metastases as the cause of death were determined postoperatively by radiographic detection of metastases or necropsy. Selection criteria for carcinomas without lymph node metastases included an invasive growth, a negative lymph node status, a histological grade III and a minimal tumor diameter above the average of the lymph node positive tumors (> 2.42 cm). All animals with non-metastatic carcinomas had a survival rate of over 24 months except animal no. 22 (2627) which developed radiographic detectable lung metastases 8 months after surgery. Tumor and lymph node histologies were evaluated independently by two board-certified pathologists, following the criteria of the WHO classification of canine mammary tumors and the Nottingham grading system. All 27 tumors were simple carcinomas and characterized by an invasive, mostly solid growth pattern, marked cellular pleomorphism, anisokaryosis and 3 or more mitotic figures per high power field.
2010-12-01 | E-GEOD-20718 | biostudies-arrayexpress
Project description:In this study, we present the first comparison of global transcriptional changes taking place in canine lymphoma and human diffuse large B-cell lymphoma (DLBCL), with particular reference to the nuclear factor-kappaB (NF-κB) pathway. Microarray data generated from lymph nodes diagnosed with canine DLBCL and healthy lymph nodes were used for differential expression analysis, co-expression analysis and pathway analysis, and compared with analysis of publicly available microarray data from human healthy and DLBCL lymph nodes. The comparisons between species at gene level were performed by mapping the probesets in canine microarrays to orthologous genes in humans and vice versa. A considerable number of differentially expressed genes between canine lymphoma and healthy lymph node samples were also found differentially expressed between human DLBCL and healthy lymph node samples. Principal component analysis (PCA) using a literature derived 120 NF-κB target gene set mapped to 199 orthologous canine array probesets and 259 human array probesets clearly separated the healthy and cancer samples in both canine and human datasets. The analysis demonstrated that for both human and canine DLBCL there is activation of the NF-κB/p65 canonical pathway rather than the alternative pathway. This has therapeutic implications for the use of specific pathway inhibitors for the treatment of DLBCL for both species and also indicates that naturally occurring canine lymphoma could be used as a model to study therapeutic strategies for human lymphoma. The model was further validated by the identification of molecular signatures that could sub-classify canine DLBCL into activated B-cell-like (ABC) or germinal centre B-cell-like (GCB) types equivalent to human subtypes.
2013-09-26 | GSE30881 | GEO