The gene expression patterns of favorable histology Wilms tumors (FHWT) that relapsed were compared with those that did not relapse using oligonucleotide arrays
Predicting relapse in favorable histology Wilms tumor using gene expression analysis: a report from the Renal Tumor Committee of the Children's Oncology Group.
No sample metadata fields
View SamplesFibroadenomas are the most common benign breast tumors in women under 30. Unlike their malignant counterparts, relatively molecular profiling has been done on fibroadenomas. Here we performed gene expression profiling on ten fibroadenomas in order to better characterize these tumors. Through targeted amplicon sequencing, we have found that six of these tumors have MED12 mutations. We show that the MED12 mutations, among others, are associated with activated estrogen signaling, as well as increased invasiveness through upregulation of ECM remodelling genes.
Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma.
Age
View SamplesSorafenib leads to a survival benefit in patients with advanced hepatocellular carcinoma but its use is hampered by the occurrence of drug resistance. To investigate the molecular mechanisms involved we developed five resistant human liver cell lines in which we studied morphology, gene expression and invasive potential. The cells changed their appearance, lost E-cadherin and KRT19 and showed high expression of vimentin, indicating epithelial-to-mesenchymal transition. Resistant cells showed reduced adherent growth, became more invasive and lost liver-specific gene expression. Furthermore, following withdrawal of sorafenib, the resistant cells showed rebound growth, a phenomenon also found in patients. This cell model was further used to investigate strategies for restoration of sensitivity to sorafenib.
Long-term exposure to sorafenib of liver cancer cells induces resistance with epithelial-to-mesenchymal transition, increased invasion and risk of rebound growth.
Cell line
View SamplesHeritable genetic variants modify cystic fibrosis (CF) clinical phenotypes, e.g., lung disease, age-of-onset of persistent Pseudomonas aeruginosa (P. aeruginosa), and meconium ileus (MI). Previous genome wide association studies (GWAS) have begun to inform the genetic architecture of CF phenotypes. Analyses of gene expression will complement GWAS, as demonstrated by analyses of gene expression in lymphoblastoid cell lines (LCLs) to identify disease-related pathophysiological processes for non-CF complex traits. In this study, global gene expression was measured in RNA from LCLs from 754 CF patients and analyzed for association with lung disease severity, age-of-onset of persistent P. aeruginosa pulmonary infection, and MI at birth. Each phenotype displayed distinct expression associations. Most pathways significantly associated with lung disease were related to membranes, vesicle traffic, and Golgi/endoplasmic reticulum (ER). Pathways containing HLA genes (Class I and II) were significantly associated with both lung and P. aeruginosa phenotypes, but they displayed qualitative differences between phenotypes. MI associated with pathways involving oxidative phosphorylation. The results support the concept that gene expression associated with heritable variation acts to modify phenotypes in CF.
Gene expression in transformed lymphocytes reveals variation in endomembrane and HLA pathways modifying cystic fibrosis pulmonary phenotypes.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma.
Specimen part, Disease, Disease stage
View SamplesType II Enteropathy-associated T-cell lymphoma (Type II EATL) is an aggressive intestinal T-cell lymphoma with poor prognosis and has not been molecularly profiled. Through targeted amplicon sequencing, we identified a large portion of Type II EATL samples that harbor mutations in the STAT5B, JAK3 and GNAI2 genes. Here we performed gene expression profiling on four Type II EATL samples in order to better characterize this disease. As Type II EATL is suggested to arise from CD8+ IELs, we integrated our data with publicly available profile of CD8 and CD8 T-cells from healthy donors (GSE33374). Gene expression profiling independently demonstrated strong enrichment of several aspects of GPCR and JAK-STAT signaling pathways. Moreover, an significant association was identified with genes containing STAT5B binding sites in their promoters.
JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma.
Specimen part
View SamplesTristetraprolin is a vertebrate CCCH tandem zinc finger protein that can bind to and destabilize certain mRNAs containing AU-rich element binding sites. zfs1 is the single gene in the fission yeast, Schizosaccharomyces pombe, that encodes a protein containing the critical features of the tristetraprolin zinc finger domain. zfs1 has been linked to pheromone signal transduction control and to the coordination of mitosis, but no biological function has been ascribed to the zfs1 protein. Through a functional genomics approach we compared transcript levels in wild-type and zfs1-deficient S. pombe strains; those elevated in the zfs1-deficient strain were examined for the presence of potential tristetraprolin-like binding sites. One such potential target transcript was encoded by arz1, a gene encoding a protein of unknown function that contains armadillo repeats. arz1 mRNA decay was inhibited in the zfs1-deficient strain when it was expressed under the control of a thiamine-repressible promoter. Mutations within one AU-rich element present in the arz1 3-untranslated region protected this transcript from zfs1-promoted decay, whereas mutating another potential binding site had no effect. Binding assays confirmed a direct interaction between zfs1 and arz1 mRNA-based probes; this interaction was eliminated when key residues were mutated in either zfs1 zinc finger. zfs1 and its targets in S. pombe represent a useful model system for studies of zinc finger protein/AU-rich element interactions that result in mRNA decay.
Characterization of zfs1 as an mRNA-binding and -destabilizing protein in Schizosaccharomyces pombe.
No sample metadata fields
View SamplesSplenic marginal zone lymphoma (SMZL) is a rare, indolent non-Hodgkin’s lymphoma that affects 0.13 per 100,000 persons annually. Overall survival of SMZL is estimated to reach 8 to 11 years in most cases, but up to 30% of SMZL cases develop aggressive presentations resulting in greatly diminished time of survival. SMZL presents with a very heterogeneous molecular profile, making diagnosis problematic and accurate prognosis even less likely. The study herein has utilized this data to assist in identifying a potential diagnostic gene expression signature with highly specific predictive utility for further evaluation among control and SMZL patient samples. Delineation of a unique SMZL signature that could provide diagnostic utility for a malignancy that has historically been difficult to identify. These results should be further investigated and validated in subsequent molecular investigations of SMZL so it may be potentially incorporated into standard oncology practice for improving the understanding and outlook for SMZL patients.
Identification of a Splenic Marginal Zone Lymphoma Signature: Preliminary Findings With Diagnostic Potential.
No sample metadata fields
View SamplesThe paraveinal mesophyll (PVM) of soybean leaves is a layer of laterally expanded cells sandwiched between the palisade and spongy mesophyll chlorenchyma. The vacuoles of PVM cells contain an abundance of a putative vegetative storage protein, VSP (, ). VSP is is constitutively produced, but is up-regulated during sink limitation experiments involving flower, fruit, or vegetative bud removal. Soybean vegetative lipoxygenases (Vlx), consisting of 5 isozymes (Vlx, A-D), have been identified as potential storage proteins because they accumulate to high levels with experimental sink limitation and have been co-localized with VSP to the vacuoles of PVM cells. We re-investigated the sub-cellular locations of these enzymes with TEM immuno-cytochemistry. We employed laser micro-dissection to compared RNA expression of PVM cells with mesophyll chlorenchyma cells, and we performed a micro-array analysis of soybean leaf samples representing a time-course, sink-limitation, experiment. We found that none of the Vlx isozymes co-localize with putative storage proteins in PVM vacuoles, and that our sink limitation experiment (typical of those used in the past) induced a strong up-regulation of stress response genes, simultaneous with the up-regulation of the Vlx isozymes. Our findings do not support a storage function for soybean Vlx.
Experimental sink removal induces stress responses, including shifts in amino acid and phenylpropanoid metabolism, in soybean leaves.
Specimen part, Disease
View SamplesThe paraveinal mesophyll (PVM) of soybean leaves is a layer of laterally expanded cells sandwiched between the palisade and spongy mesophyll chlorenchyma. The vacuoles of PVM cells contain an abundance of a putative vegetative storage protein, VSP (, ). VSP is is constitutively produced, but is up-regulated during sink limitation experiments involving flower, fruit, or vegetative bud removal. Soybean vegetative lipoxygenases (Vlx), consisting of 5 isozymes (Vlx, A-D), have been identified as potential storage proteins because they accumulate to high levels with experimental sink limitation and have been co-localized with VSP to the vacuoles of PVM cells. We re-investigated the sub-cellular locations of these enzymes with TEM immuno-cytochemistry. We employed laser micro-dissection to compared RNA expression of PVM cells with mesophyll chlorenchyma cells; and we performed a micro-array analysis of soybean leaf samples representing a time-course, sink-limitation, experiment. We found that none of the Vlx isozymes co-localize with putative storage proteins in PVM vacuoles, and that our sink limitation experiment (typical of those used in the past) induced a strong up-regulation of stress response genes, simultaneous with the up-regulation of the Vlx isozymes. Our findings do not support a storage function for soybean Vlx.
Experimental sink removal induces stress responses, including shifts in amino acid and phenylpropanoid metabolism, in soybean leaves.
Specimen part
View Samples