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GSE63967
Mus musculus
109 Downloadable Samples
Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Human tumours show a high level of clonal heterogeneity that contributes to malignant progression and metastasis, but the processes that influence the timing of metastatic dissemination of subclones are unknown. Here, we have used whole exome sequencing of 98 matched benign, malignant, and metastatic skin tumours from genetically heterogeneous mice to demonstrate that most metastases disseminate synchronously from the primary tumour, but then evolve separately, acquiring an additional set of mutations during growth at distant sites. Shared mutations between primary carcinomas and their matched metastases have the distinct A>T signature of the initiating carcinogen Dimethylbanzanthracene (DMBA), but non-shared mutations are primarily G>T or C>T substitutions, associated with oxidative stress. We found recurrent point mutations in several hundred genes, including several in the Ras (Hras, Kras, and Pik3ca) pathway. We propose that carcinogen-driven mouse tumour models can aid our understanding of the forces that shape clonal and genetic evolution of human cancers.
Publication Title
Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Effect of SDHB silencing using siRNA methodologies in the tumor phenotype
Publication Title
Cells silenced for SDHB expression display characteristic features of the tumor phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 161 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
When making treatment decisions, oncologists often stratify breast cancers into a low-risk group (ER+, low grade); an intermediate-risk group (ER+, high grade); and a high-risk group that includes Her2+ and triple-negative (ER-/PR-/Her2-) tumors. None of the currently available gene signatures correlates to this clinical classification. We aimed to develop a test that is practical for the oncologists, that offers both molecular characterization of BCs, and improved prediction of prognosis and treatment response. We investigated the molecular basis of such clinical practice by grouping Her2+ and triple-negative breast cancers together during clustering analyses on the genome-wide gene expression profiles of our training cohort, mostly derived from fine needle aspiration biopsies (FNABs) of 149 consecutive evaluable Breast cancers. The analyses consistently divided these tumors into a three-cluster pattern, similar to clinical risk-stratification groups, that was reproducible in published microarray databases (n=2487) annotated with clinical outcomes. The clinicopathologic parameters of each of these three molecular groups were also similar to clinical classification. The low-risk group had good outcomes and benefited from endocrine therapy. Both intermediate- and high-risk groups had poor outcomes and were resistant to endocrine therapy. The latter demonstrated the highest rate of complete pathological response to neoadjuvant chemotherapy; the highest activities in MYC, E2F1, Ras, -Catenin and IFN- pathways; and poor prognosis predicted by 14 independent prognostic signatures. Based on a multivariate analysis, this new gene signature, termed ClinicoMolecular Triad Classification, predicted recurrence and treatment response better than all pathologic parameters and other prognostic signatures.
Publication Title
A new gene expression signature, the ClinicoMolecular Triad Classification, may improve prediction and prognostication of breast cancer at the time of diagnosis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
To measures the comparability and concordance of Illumina microarray, a series of 30 samples of Universal Human Reference RNA (UHRR) were set as controls for every single chip of total 30 Human-Ref V2 BeadChips. The average bead number of the 30 arrays was 42.38.1 for any bead type over the 22,184 probes. A high average correlation coefficient (r) value was obtained as 0.99080077 relative to each other of the expression intensity values from the 30 duplicate UHRR samples.
Publication Title
A new gene expression signature, the ClinicoMolecular Triad Classification, may improve prediction and prognostication of breast cancer at the time of diagnosis.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Adipose stroma in the mouse mammary gland undergoes remodeling throughout the 5 stages of development. These include nulliparous (virgin;never been pregnant), pregnant, lactating, involuting and regressed.
Publication Title
Pregnancy-associated breast cancers are driven by differences in adipose stromal cells present during lactation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
Illumina HiSeq 2000
Description
Purpose: Identification of relevant genetic pathways that are altered with aging knowing that the precursors for bone-forming osteoblasts reside in the mesenchymal cell population of bone marrow. Method: harvested and characterized, without in vitro culture, mesenchymal cells form human bone marrow capable of osteogenic differentiation Results: Identification of differentially regulated genes with aging in a highly enriched human bone marrow mesenchymal cell population. Conclusions: we have for the first time identified age-related differential gene expression and DNA methylation patterns in a highly enriched human bone marrow mesenchymal cell populationprofiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions. Overall design: Examination of gene expression and DNA methylation patterns from a highly enriched bone marrow mesenchymal cell population from young (mean age, 28.7 years) versus old (mean age, 73.3 years) women
Publication Title
Global transcriptional profiling using RNA sequencing and DNA methylation patterns in highly enriched mesenchymal cells from young versus elderly women.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Infection is a major complication and cause of mortality and morbidity after acute stroke however the mechanisms are poorly understood. After experimental stroke the microarchitecture and cellular composition of the spleen are extensively disrupted resulting in deficits to immune function.
Publication Title
Experimental Stroke Differentially Affects Discrete Subpopulations of Splenic Macrophages.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
We access the activity-dependent genes in olfactory neuron cells with unilateral naris occlusion model with mouse. Overall design: mRNA profile of olfactory epithelia between closed and open sides of mice naris was compared
Publication Title
Activity-Dependent Gene Expression in the Mammalian Olfactory Epithelium.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 398 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The analytical validation of a 15 gene prognostic signature for early-stage, completely resected, non-small-cell lung carcinoma that distinguishes between patients with good and poor prognoses.
Publication Title
Analytical Performance of a 15-Gene Prognostic Assay for Early-Stage Non-Small-Cell Lung Carcinoma Using RNA-Stabilized Tissue.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 758 Downloadable Samples
- Illumina HiSeq 2500
Description
Genetic variation modulating risk of sporadic Parkinson's disease (PD) has been primarily explored through genome wide association studies (GWAS). However, like many other common genetic diseases, the impacted genes remain largely unknown. Here, we used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal timepoints. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a novel postnatal neuroblast population and substantia nigra (SN) DA neurons. We use these population-specific data to develop a scoring system to prioritize candidate genes in all 49 GWAS intervals implicated in PD risk, including known PD genes and many with extensive supporting literature. As proof of principle, we confirm that the nigrostriatal pathway is compromised in Cplx1 null mice. Ultimately, this systematic approach establishes biologically pertinent candidates and testable hypotheses for sporadic PD, informing a new era of PD genetic research. Overall design: 473 single cell RNA-Seq samples from sorted mouse Th-eGFP+ dopaminergic neurons collected at two timepoints from three distinct brain regions.
Publication Title
Single-Cell RNA-Seq of Mouse Dopaminergic Neurons Informs Candidate Gene Selection for Sporadic Parkinson Disease.
Sample Metadata Fields
Specimen part, Subject
View Samples