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GSE41599
Homo sapiens
27 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Transcriptome profile of highly purified multipotential (P), erythroid (E), and myeloid (M) bone marrow progenitors from three RPS19 mutated Diamond-Blackfan anemia and six control human subjects.
Publication Title
Defective ribosomal protein gene expression alters transcription, translation, apoptosis, and oncogenic pathways in Diamond-Blackfan anemia.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 162 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
These arrays are used for various projects
Publication Title
DNA amplification is a ubiquitous mechanism of oncogene activation in lung and other cancers.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 22 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression.
Sample Metadata Fields
Sex, Age, Specimen part, Race, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Gene expression profiling of 60 lung adenocarcinoma tumors and their matched histologically normal adjacent lung tissue samples were analyzed using Illumina HumanWG-6 v3.0 expression beadchip. We integrated these data with DNA methylation profiles of the same samples to identify potential DNA methylation regulated genes.
Publication Title
Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression.
Sample Metadata Fields
Sex, Age, Specimen part, Race, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression analysis from erythroid progenitors (CD34+/CD71(high)/CD45- mononuclear cells from the bone marrow) of patients with Diamond-Blackfan anemia (due to RPS19 mutations) and control individuals.
Publication Title
Altered translation of GATA1 in Diamond-Blackfan anemia.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 15 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We have developed cdk4/hTERT-immortalized normal human bronchial epithelial cells (HBECs) to study lung cancer pathogenesis. By studying the oncogenic effect of common lung cancer alterations (p53, KRAS, and c-MYC) we demonstrate the ability of this model to characterize the stepwise transformation of bronchial epithelial cells to full malignancy. Using HBECs derived from multiple individuals we found: 1) the combination of five genetic alterations (p53, KRASV12, c-MYC, CDK4 and hTERT) is sufficient for full tumorigenic conversion of HBECs; 2) high levels of KRASV12 are required for full malignant transformation of HBECs, however these levels also stimulate oncogene-induced senescence; 3) RAS-induced senescence is largely bypassed with loss of p53 function; 4) over-expression of c-MYC greatly enhances malignancy but only in the context of sh-p53+KRASV12; 5) HBECs from different individuals vary in their sensitivity to transformation by these oncogenic manipulations; 6) serum-induced epithelial-to-mesenchymal transition (EMT) increases in vivo tumorigenicity; 7) genetically-identical clones of transformed HBECs exhibit pronounced differences in tumor growth, histology, and differentiation as well as sensitivity to standard platinum-based chemotherapies; and 8) an mRNA signature derived from tumorigenic and non-tumorigenic clones is predictive of outcome in lung cancer patients. Collectively, we demonstrate this HBEC model system can be used to study the effect of oncogenic mutations on malignant progression, oncogene-induced senescence, and EMT along with clinically translatable applications such as development of prognostic signatures and drug response phenotypes.
Publication Title
Human lung epithelial cells progressed to malignancy through specific oncogenic manipulations.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify the global gene expression changes driven by L-Myc during SCLC development, mRNA expression profiles were compared using total RNAs from preneoplastic precursors of SCLC and the cells transformed by overexpression of L-Myc.
Publication Title
Genetic requirement for Mycl and efficacy of RNA Pol I inhibition in mouse models of small cell lung cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Diamond Blackfan anemia is a congenital bone marrow failure syndrome characterized by hypoproliferative anemia, often with associated physical abnormalities. Perturbations of the ribosome appear critically important to the development of DBA, as alterations in 9 different ribosomal protein genes have been identified in multiple unrelated families, along with rarer abnormalities of additional ribosomal proteins. However, presently only 50-60% of patients have an identifiable genetic lesion by ribosomal protein gene sequencing. Using genome-wide SNP array to evaluate for regions of recurrent copy variation, we identified 2 patients with mosaic loss in the region of the the chromosome 5-deleted region involved in somatically-acquired 5q- myelodysplastic syndrome.
Publication Title
Diminutive somatic deletions in the 5q region lead to a phenotype atypical of classical 5q- syndrome.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Using an in vitro model for malignant transformation of human bronchial epithelial cells (HBECs) we have found epithelial-to-mesenchymal transition (EMT) and expression of the EMT-transcription factor ZEB1 are early and critical events. Specifically, we found preexisting oncogenic mutations in TP53 and KRAS were required for HBECs to engage EMT machinery in response to microenvironmental (serum/TGF) or specific oncogenetic (MYC) EMT-inducing factors, which induce EMT through distinct TGF-dependent and vitamin D receptor (VDR)-dependent pathways, respectively, with both requiring ZEB1. Functional studies demonstrated ZEB1 causally promotes the malignant progression of HBECs and tumorigenicity of NSCLC and small cell lung cancer (SCLC) lines. Mechanistically ZEB1 directly represses ESRP1 leading to increased mesenchymal splicing of CD44, which drives a switch to CD44hi status and defines a highly transformed subpopulation. This was supported by finding ZEB1 is expressed in early-stage primary non-small cell lung cancers (NSCLC), as early as stage IB tumors, and its expression correlates with TNM stage. We conclude that: ZEB1-induced EMT and associated ESRP1 and CD44 molecular changes are important biomarkers for lung cancer pathogenesis; TGF and VDR are EMT chemoprevention targets; and as such, ZEB1 represents an important therapeutic target in NSCLC and SCLC.
Publication Title
ZEB1 drives epithelial-to-mesenchymal transition in lung cancer.
Sample Metadata Fields
Sex, Age, Cell line
View Samples- Homo sapiens
- 20 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Affymetrix Genome-Wide Human SNP 6.0 Array (genomewidesnp6)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A comprehensively characterized cell line panel highly representative of clinical ovarian high-grade serous carcinomas.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples