Mouse lung cancers were generated using the KrasLA model, in which a latent mutated Kras2 allele (resulting in the amino acid substitution G12D) is sporadically activated through spontaneous homologous recombination. These mice develop lung adenomas with full penetrance; over time, the tumors acquire morphologic characteristics reminiscent of those of human adenocarcinoma, such as nuclear atypia and a high mitotic index.
An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis.
Specimen part
View SamplesDNA methylation, at CpG islands and promoters, is often inversely correlated with gene expression.
The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts.
Specimen part, Cell line
View SamplesDNA methylation is often inversely correlated with gene expression.
Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts.
Cell line
View SamplesPurpose: The JBR.10 trial demonstrated benefit from adjuvant cisplatin/vinorelbine (ACT) in early-stage non-small-cell lung cancer (NSCLC). We hypothesized that expression profiling may identify stage-independent subgroups who might benefit from ACT.
Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer.
Sex, Age, Specimen part
View SamplesA key step in bringing gene expression data into clinical practice is the conduct of large studies to confirm preliminary models. The performance of such confirmatory studies and the transition to clinical practice requires that microarray data from different laboratories are comparable and reproducible. We designed a study to assess the comparability of data from four laboratories that will conduct a larger microarray profiling confirmation project in lung adenocarcinomas. To test the feasibility of combining data across laboratories, frozen tumor tissues, cell line pellets, and purified RNA samples were analyzed at each of the four laboratories. Samples of each type and several subsamples from each tumor and each cell line were blinded before being distributed. The laboratories followed a common protocol for all steps of tissue processing, RNA extraction, and microarray analysis using Affymetrix Human Genome U133A arrays. High within-laboratory and between-laboratory correlations were observed on the purified RNA samples, the cell lines, and the frozen tumor tissues. Intraclass correlation within laboratories was only slightly stronger than between laboratories, and the intraclass correlation tended to be weakest for genes expressed at low levels and showing small variation. Finally, hierarchical cluster analysis revealed that the repeated samples clustered together regardless of the laboratory in which the experiments were done. The findings indicate that under properly controlled conditions it is feasible to perform complete tumor microarray analysis, from tissue processing to hybridization and scanning, at multiple independent laboratories for a single study.
Interlaboratory comparability study of cancer gene expression analysis using oligonucleotide microarrays.
Sex, Age, Specimen part, Disease, Disease stage, Cell line
View SamplesHere we report a large, training*testing, multi-site, blinded validation study to characterize the performance of several prognostic models based on gene expression for 442 lung adenocarcinomas. The hypotheses proposed examined whether microarray measurements of gene expression either alone or combined with basic clinical covariates (stage, age, sex) could be used to predict overall survival in lung cancer subjects. Several models examined produced risk scores that substantially correlated with actual subject outcome. Most methods performed better with clinical data, supporting the combined use of clinical and molecular information when building prognostic models for early-stage lung cancer. This study also provides the largest available set of microarray data with extensive pathological and clinical annotation for lung adenocarcinomas.
Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study.
Sex, Age, Specimen part, Disease, Disease stage, Race
View SamplesMembers of the CUG-BP, Elav-like family (CELF) regulate alternative splicing in the heart. In MHC-CELFdelta transgenic mice, CELF splicing activity is inhibited postnatally in heart muscle via expression of a nuclear dominant negative CELF protein under an a-myosin heavy chain promoter. MHC-CELFdelta mice develop dilated cardiomyopathy characterized by alternative splicing defects, enlarged hearts, and severe contractile dysfunction. In this study, gene expression profiles in the hearts of wild type, high- and low-expressing lines of MHC-CELFdelta mice were compared using microarrays. Gene ontology and pathway analyses identified contraction and calcium signaling as the most affected processes. Network analysis revealed that the serum response factor (SRF) network is highly affected. Downstream targets of SRF were up-regulated in MHC-CELFdelta mice compared to the wild type, suggesting an increase in SRF activity. Although SRF levels remained unchanged, known inhibitors of SRF activity were down-regulated. These results suggest a role for CELF-mediated alternative splicing in the regulation of contractile gene expression, achieved in part through modulating the activity of SRF, a key cardiac transcription factor.
Gene expression analyses implicate an alternative splicing program in regulating contractile gene expression and serum response factor activity in mice.
Sex, Age, Specimen part
View SamplesWe report on the regulation of transcripts following siRNA-mediated depletion of an RNA binding protein, CELF1, in primary chicken embryonic cardiomyocytes in culture. Overall design: Cultured chicken primary embryonic cardiomyocytes (isolated from embryonic day 8 hearts) were transfected with siRNA against CELF1 (n=3) or mock transfected (n=3) at 24 hours in culture.
Identification of Targets of CUG-BP, Elav-Like Family Member 1 (CELF1) Regulation in Embryonic Heart Muscle.
Specimen part, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup.
Specimen part
View Samples