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Homo sapiens
26 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Approximately 5% of all breast cancers can be attributed to an inherited mutation in one of two cancer susceptibility genes, BRCA1 and BRCA2. We searched for genes that have the potential to distinguish healthy BRCA1 and BRCA2 mutation carriers from non-carriers based on differences in expression profiling. Using expression microarrays we compared gene expression of irradiated lymphocytes from BRCA1 and BRCA2 mutation carriers versus control non-carriers. We identified 137 probe sets in BRCA1 carriers and 1345 in BRCA2 carriers with differential gene expression. Gene Ontology analysis revealed that most of these genes relate to regulation pathways of DNA repair processes, cell cycle regulation and apoptosis. Real-time PCR was performed on the 36 genes which were most prominently differentially expressed in the microarray assay; 21 genes were shown to be significantly differentially expressed in BRCA1 or BRCA2 mutation carriers as compared to controls (p<0.05). Based on a validation study with 40 mutation carriers and 17 non-carriers, a multiplex model that included six or more coincidental genes of 18 selected genes was constructed in order to predict the risk of carrying a mutation. The results using this model showed sensitivity 95% and specificity 88%. In summary, our study provides insight into the biological effect of heterozygous mutations in BRCA1 and BRCA2 genes in response to ionizing irradiation induced DNA damage. We also suggest a set of 18 genes that can be used as a prediction and screening tool for BRCA1 or BRCA2 mutational carriers by using easily obtained lymphocytes.
Publication Title
Determination of molecular markers for BRCA1 and BRCA2 heterozygosity using gene expression profiling.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 146 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Ph-negative myeloproliferative neoplasms (MPNs) are characterized by many somatic mutations which have already been shown useful in the prognostic assessment of MPN patients. Moreover, aberrant microRNA (miRNA) expression seems to add to the molecular complexity of MPNs, as specific miRNA signatures capable of discriminating MPN cells from those of normal donors were previously reported. In order to have a comprehensive picture of miRNA deregulation and its relationship with differential gene expression in primary myelofibrosis (PMF) cells, we obtained gene- (GEP) and miRNA expression profiles (miEP) of CD34+ cells from 31 healthy donors and 42 PMF patients using Affymetrix technology (HG-U219 and miRNA 2.0 arrays). Differentially expressed genes (DEG) and miRNAs (DEM) were sorted out by means of Partek Genomic Suite vs 6.6. Since each miRNA can target many mRNAs while a single mRNA can be targeted by multiple miRNAs, we performed Integrative Analysis (IA) by means of Ingenuity Pathway Analysis (IPA) to untangle this combinatorial complexity. In particular, IPA points out DEM-DEG pairs among experimentally validated interactions from TarBase, miRecords and Ingenuity Expert Findings as well as predicted microRNA-mRNA interactions from TargetScan. IPA microRNA Target Filter was then employed to select only the DEM-DEG pairs showing an anti-correlated expression pattern and to build regulatory networks. Finally, 3'UTR luciferase reporter assays were performed to validate IPA predicted miRNA-mRNA interactions.
Publication Title
miRNA-mRNA integrative analysis in primary myelofibrosis CD34+ cells: role of miR-155/JARID2 axis in abnormal megakaryopoiesis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
JARID2 is a chromatin remodeler, member of the Jumonji family of transcription factor genes that belongs to the polycomb repressive complex 2 (PRC2) (Peng JC et al. Cell 2009) and is frequently deleted in leukemic transformation of chronic myeloid malignancies (Puda A et al. Am J Hematol. 2012). In this work, we compared gene expression profile (GEP) of CD34+ cells from Primary Myelofibrosis (PMF) patients with healthy donors and we found JARID2 among downregulated genes. In addition, integrative analysis of gene and miRNA profiles highlighted JARID2 as a shared target of several miRNAs aberrantly expressed in PMF CD34+ cells. Since the role of JARID2 in normal and malignant hematopoiesis has never been investigated, we performed JARID2 silencing experiments on normal Cord Blood (CB) CD34+ cells to evaluate its involvement in proliferation and commitment. Therefore, CD34+ cells were transfected with a mixture of 3 Silencer Select siRNAs targeting JARID2 mRNA and with a non-targeting siRNA as control (NegCTR). The expression level of JARID2 in control samples and JARID2-siRNA cells was assessed by QRT-PCR at 24h (RQ 0,2 SEM 0,036, p <.001) and 48h (RQ 0,32 SEM 0,026, p<.001) after the last nucleofection.
Publication Title
miRNA-mRNA integrative analysis in primary myelofibrosis CD34+ cells: role of miR-155/JARID2 axis in abnormal megakaryopoiesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
This study was designed to compare the global gene expression change induced by the circulating, prodomain bound forms of BMP9 and BMP10 (pro-BMP9 and pro-BMP10) in human pulmonary arterial endothelial cells (PAECs). This is different from many previous studies which used the growth factor domain of BMP9 and/or BMP10.
Publication Title
Molecular basis of ALK1-mediated signalling by BMP9/BMP10 and their prodomain-bound forms.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
GS-5759 is a bifunctional ligand composed of a quinolinone-containing pharmacophore found in several 2-adrenoceptor agonists linked covalently to a phosphodiesterase 4 inhibitor (PDE4) related to GSK 256066 by a pent-1-yn-1-ylbenzene spacer. The object of the study was to detemine if gene expression changes induced by GS-5759 were replicated by a 2-adrenoceptor agonist (indacaterol; Ind) and a PDE4 inhibitor (GSK 256066; GSK) in combination.
Publication Title
GS-5759, a Bifunctional β2-Adrenoceptor Agonist and Phosphodiesterase 4 Inhibitor for Chronic Obstructive Pulmonary Disease with a Unique Mode of Action: Effects on Gene Expression in Human Airway Epithelial Cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
Intracranial B16 melanoma tumors isolated from C57Bl6 mice were analyzed by mRNAseq. Four experimental groups were analyzed: (1) Mice with intracranial tumors receiving IgG; (2) Mice with intracranial tumors receiving anti-PD-1 plus anti-CTLA-4 therapy; (3) Mice with intracranial plus extracranial tumors receiving IgG; (4) Mice with intracranial plus extracranial tumors receiving anti-PD-1 plus anti-CTLA-4 therapy. Taggart et al., PNAS 2018; Overall design: mRNAseq profiles of intracranial B16 tumours at day 9 post-cancer cell implantation were generated for 4 different experimental groups (biological triplicates)
Publication Title
Anti-PD-1/anti-CTLA-4 efficacy in melanoma brain metastases depends on extracranial disease and augmentation of CD8<sup>+</sup> T cell trafficking.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 134 Downloadable Samples
- Illumina HiSeq 2500
Description
Profound changes in cancer cell identity can alter malignant potential and therapeutic response. Loss of the pulmonary lineage specifier NKX2-1 augments the growth of KRAS-driven lung adenocarcinoma and causes pulmonary to gastric transdifferentiation. Here we show that the transcription factors FoxA1 and FoxA2 are required for initiation of mucinous NKX2-1-negative lung adenocarcinomas in the mouse and for activation of their gastric differentiation program. Foxa1/2 deletion severely impairs tumor initiation and causes a proximal shift in cellular identity, yielding tumors expressing markers of the squamocolumnar junction of the gastrointestinal tract. In contrast, stochastic loss of FoxA1/2 expression in NKX2-1-negative tumors is associated with keratinizing squamous differentiation. Using sequential in vivo recombination, we find that FoxA1/2 loss in established KRAS-driven neoplasia is sufficient for direct induction of keratinizing squamous cell carcinomas in the lung. Thus, NKX2-1, FoxA1 and FoxA2 coordinately regulate the growth and identity of lung adenocarcinoma in a context-specific manner. Overall design: Murine lung tumor cells of differing genotypes were isolated by FACS and subjected to single cell analysis using the Fluidigm C1 platform.
Publication Title
FoxA1 and FoxA2 drive gastric differentiation and suppress squamous identity in NKX2-1-negative lung cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 17 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Lung cancers exhibit pronounced functional heterogeneity, confounding precision medicine. We studied how the cell-of-origin contributes to phenotypic heterogeneity following conditional expression of KrasG12D and loss of Lkb1 (Kras;Lkb1). Using progenitor cell type-restricted adenoviral-Cre to target cells expressing Surfactant Protein C (SPC) or club cell antigen 10 (CC10), we show that Ad5-CC10-Cre infected mice exhibit a shorter latency compared with Ad5-SPC-Cre cohorts. We further demonstrate that CC10+ cells are the predominant progenitors of adenosquamous carcinoma (ASC) tumors, and give rise to a wider spectrum of histotypes that includes mucinous and acinar adenocarcinomas. Transcriptome analysis shows ASC histotype-specific upregulation of proinflammatory and immunomodulatory genes. This is accompanied with an ASC-specific immunosuppressive environment, consisting of downregulated MHC genes, recruitment of CD11b+ Gr-1+ tumor-associated neutrophils (TANs) and decreased T-cell numbers. We conclude that progenitor cell-specific etiology influences the Kras;Lkb1-driven tumor histopathology spectrum and histotype-specific immune microenvironment.
Publication Title
Cell of Origin Links Histotype Spectrum to Immune Microenvironment Diversity in Non-small-Cell Lung Cancer Driven by Mutant Kras and Loss of Lkb1.
Sample Metadata Fields
Specimen part
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GSE63334- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This study was designed to investigate the transcripts that are regulated by Twist1 in skin tymor epithelial cells in a p53-dependent and independent manner. To this aim, Tumor epithelial cells from primary mouse skin tumors of different genotypes were FACS sorted and analyzed by microarray.
Publication Title
Different levels of Twist1 regulate skin tumor initiation, stemness, and progression.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
microRNA-126 is a microRNA predominately expressed by endothelial cells and controls angiogenesis. Unexpectedly, we found that mice deficient in miR-126 have a major impairment in their innate response to pathogen-associated nucleic acids, as well as HIV, which results in more widespread cell infection. Further examination revealed that this was due to miR-126 control of plasmacytoid DC (pDC) homeostasis and function, and that miR-126 regulates expression of TLR7, TLR9, NFkB1 and other innate response genes, as well as VEGF-receptor 2 (VEGFR2). Deletion of VEGFR2 on DCs resulted in reduced interferon production, supporting a role for VEGFR2 in miR-126 regulation of pDCs. These studies identify the miR-126/VEGFR2 axis as an important regulator of the innate response that operates through multiscale control of pDCs.
Publication Title
The miR-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids.
Sample Metadata Fields
Age, Specimen part
View Samples