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E-MTAB-991
Homo sapiens
115 Downloadable Samples
Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Patient-derived xenograft models are considered to represent the heterogeneity of human cancers and might be more relevant preclinical models to evaluate effective therapeutic agents. Our consortium joins efforts to extensively develop and characterize a new collection of patient-derived colorectal cancer models. From 86 unsupervised surgical colon sample collection, 54 tumors were successfully xenografted in immunodeficient mice and rats, representing 35 primary tumors, 5 peritoneal carcinosis and 14 metastases. Our histological and molecular characterization of patient tumors, first passage on mice and later passages includes the sequence of key genes involved in CRC (ie APC, KRAS, TP53), CGH array and transcriptomic analysis. This comprehensive characterization demonstrates that our collection recapitulates the clinical situation regarding the histopathological and molecular diversity of colorectal cancers. Moreover, patient tumors and corresponding models are clustering together which gives the opportunity to look for relevant signatures and comparison studies between clinical and preclinical data. Hence, we performed pharmacological monotherapy studies with standard of care for colon cancer (5-FU, oxaliplatin, irinotecan, cetuximab). Through this extensive in vivo analysis, we have compared the molecular profile with the drug sensitivity of each tumor models, and run an equivalent of a cetuximab phase II clinical trial in a preclinical setting. Our results confirm the key role of KRAS mutation in the cetuximab resistance and demonstrate that such collection could bring benefit to evaluate novel targeted therapeutic strategies and potentially help the stratification strategy for cancer patients according to molecular marker. This set correspond to 82 CGH profiles, with 7 samples from patient tumor and 75 samples from mouse xenograft at different passages P0 to P9. All hybridizations are performed with Human CGH 244K Agilent arrays (amadid 014693) in dual color with Human DNA Promega (sex matched) as reference. ID for biosources without an -Px suffix correspond to tumor patients. ID with a suffix correspond to xenograft with 0 for the first passage.
Publication Title
Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Time
View Samples- Pseudomonas aeruginosa
- 6 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Several bacterial human pathogens regulate the production of virulence factors by temperature, expressing them only at 37 C. Accordingly we show that the production of all P. aeruginosa virulence factors that are dependent on the QS transcriptional regulator RhlR, but only a fraction that are activated by LasR, are induced at 37 C compared to 30 C or 25 C. The RhlR-dependent induction at 37 C is a posttranscriptional effect due to an RNA thermometer of the ROSE family that thermoregulates the expression of rhlAB operon involved in rhamnolipids production, a virulence associated trait. This RNA structure also affects the expression of the downstream rhlR gene. A second thermometer is present upstream lasI and causes a reduced expression of this gene at lower temperatures without causing a significant decrease of the autoinducer 3-oxo-dodecanoyl homoserine lactone.
Publication Title
Regulation of Pseudomonas aeruginosa virulence factors by two novel RNA thermometers.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 51 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Correlate the gene expression profiles with the most relevant patterns of chromosome abnormalities (cytogenetic subgroups of meningiomas) and the gene expression profiles could help to explain the differences in clinical behaviour of meningiomas.
Publication Title
Gene expression profiles of meningiomas are associated with tumor cytogenetics and patient outcome.
Sample Metadata Fields
Sex, Age, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Bisphenol-A is a widespread endocrine disruptor chemical. In utero or perinatal exposure to bisphenol-A (BPA), leads to impaired glucose metabolism during adulthood. To investigate the consequences of the exposure to bisphenol-A during development in pancreatic beta-cell growth
Publication Title
Maternal Exposure to Bisphenol-A During Pregnancy Increases Pancreatic β-Cell Growth During Early Life in Male Mice Offspring.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 57 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Choroid plexus carcinomas (CPC) are poorly understood and frequently lethal brain tumors with minimal treatment options. Using a new mouse model of the disease and a large cohort of human CPCs [GSE60892; GSE60899], we performed a cross-species, genome-wide search for novel oncogenes within syntenic regions of chromosome gain. TAF12, NFYC and RAD54L, co-located on human chromosome 1p32-35.3 and mouse chromosome 4qD1-D3, were identified as oncogenes that are gained in tumors in both species and required to initiate and progress the disease in mice. TAF12 and NFYC are transcription factors that regulate the epigenome, while RAD54L plays a central role in DNA repair. Our data identify a group of concurrently gained, novel oncogenes that cooperate in the formation of CPC and unmask potential new avenues for therapy.
Publication Title
Cross-Species Genomics Identifies TAF12, NFYC, and RAD54L as Choroid Plexus Carcinoma Oncogenes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
UOK257 cell line was derived from a BHD patient. It harbors a germline mutation in FLCN (c.1285dupC) and LOH. UOK257-2 cells were generated from UOK257 cells by introducing wildtype FLCN using retrovirus. FLCN inactivation induces TFE3 transcriptional activity by increasing its nuclear localization. Thus expression microarray was used to identify the genes regulated by FLCN and TFE3.
Publication Title
The UOK 257 cell line: a novel model for studies of the human Birt-Hogg-Dubé gene pathway.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 135 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Previous studies have shown that ischemia alters gene expression in normal and malignant tissues. There are no studies that evaluated effects of ischemia in renal tumors. This study examines the impact of ischemia and tissue procurement conditions on RNA integrity and gene expression in renal cell carcinoma.
Publication Title
Impact of ischemia and procurement conditions on gene expression in renal cell carcinoma.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
We sequenced mRNA from triplicate log-phase cultures of BY4741 (WT) transformed with pRS313-HA3-SSN6 and taf14D transformed with pRS313-HA3-SSN6 (empty vector), full-length pRS313-TAF14-HA3-SSN6, or pRS313-taf14W81A-HA3-SSN6 cultured in synthetic complete media lacking histidine. Overall design: Examination of changes in gene expression when the YEATS domain of Taf14 is mutated so it cannot bind acetyl-H3.
Publication Title
Association of Taf14 with acetylated histone H3 directs gene transcription and the DNA damage response.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
Huntington neurodegenerative disease (HD) is associated with extensive down-regulation of neuronal genes. We show preferential down-regulation of super-enhancer-regulated neuronal function genes in the striatum of HD mice. Striatal super-enhancers display extensive H3K27 acetylation within gene bodies and drive transcription characterized by low levels of paused RNAPII. Down-regulation of gene expression is associated with diminished H3K27 acetylation and RNAPII recruitment. Striatal super-enhancers are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Thus, enhancer topography and transcription dynamics are major parameters determining the propensity of a gene to be deregulated in a neurodegenerative disease. Overall design: RNA profiles in Striatum of WT and R6/1 mice by deep sequencing using Illumina HiSeq 2000.
Publication Title
Altered enhancer transcription underlies Huntington's disease striatal transcriptional signature.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Background and aims: Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. Incidence is increasing worldwide and these cancers collectively represent the second most common primary liver tumour. CCAs are characterized by genetic and epigenetic alterations that determine their pathogenesis. Hypermethylation of the SOX17 promoter was recently reported in human CCA tumours. SOX17 seems to be a key transcription factor for biliary embryogenesis. Here, we evaluated the role of SOX17 in cholangiocyte differentiation and in cholangiocarcinogenesis. Methods: SOX17 expression and function was evaluated during the differentiation of human induced pluripotent stem cells (iPSC) into cholangiocytes, in the dedifferentiation of normal human cholangiocytes (NHC) and in cholangiocarcinogenesis. Lentiviruses overexpressing or knocking-down SOX17 (Lent-SOX17 and Lent-shRNA-SOX17, respectively) were used. Gene expression arrays were performed. Results: SOX17 expression is highly induced in the later stages of cholangiocyte differentiation from iPSC, and mediates the acquisition of the biliary markers cytokeratin (CK) 7 and 19, as well as fibronectin. In addition, SOX17 becomes progressively downregulated in NHC over serial cell passages in vitro and this event is associated with cellular senescence; however, experimental SOX17 knocking-down in differentiated NHC decreased the expression of both CK7 and 19 without affecting cellular senescence. SOX17 expression is reduced in CCA cells compared to NHC, as well as in human CCA tissue compared to human gallbladder tissue or NHC. In a murine xenograft model, overexpression of SOX17 in CCA cells decreased their tumorigenic capacity related to increased oxidative stress and apoptosis. Interestingly, overexpression of SOX17 in NHC did not affect their survival. Moreover, SOX17 overexpression inhibited the Wnt/-catenin-dependent proliferation in CCA cells and was associated with upregulation of biliary epithelial markers and restoration of the primary cilium length. Both Wnt3a and TGF1 decreased SOX17 expression in NHC in a DNMT1-dependent manner. Inhibition of DNMT1 in CCA cells with siRNAs or pharmacological drugs upregulated SOX17 expression. Conclusion: SOX17 regulates the cholangiocyte phenotype and becomes epigenetically downregulated in CCA. SOX17 acts as a tumour suppressor in CCA, and restoration of its expression may have important therapeutic value.
Publication Title
SOX17 regulates cholangiocyte differentiation and acts as a tumor suppressor in cholangiocarcinoma.
Sample Metadata Fields
Specimen part, Treatment
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