This work was conducted to identify shared and specific target genes of different ETS transcription factor rearrangements in prostate cancer. Potential target genes were identified by differential gene expression analysis of primary tumor samples with ETS rearrangements, and validated by ETS silencing in prostate cancer cell lines.
Molecular subtyping of primary prostate cancer reveals specific and shared target genes of different ETS rearrangements.
Specimen part
View SamplesArabinogalactan proteins are proteoglycans known to have important roles during cell growth and development, namelly during pollen tube growth.
No associated publication
Specimen part, Time
View SamplesThe most frequent genetic alterations in melanoma are gain-of-function mutations in BRAF, which result in addiction to the RAF-MEK-ERK signaling pathway. Despite success of RAF and MEK inhibitors in treating BRAFV600 mutant tumors, a major challenge is the inevitable emergence of drug resistance, which often involves reactivation of the MAPK pathway. Interestingly, resistant tumors are often sensitive to drug withdrawal, suggesting that hyperactivation of the MAPK pathway is not tolerated. To further characterize this phenomenon, we generated isogenic models of inducible MAPK hyperactivation in BRAFV600E melanoma cells by overexpression of ERK2. Using this model system, we demonstrated that supra-physiological levels of MAPK signaling led to cell death, which was reversed by MAPK inhibitors. Whereas MAPK pathway inhibition led to cell stasis in BRAFV600E melanoma cells, MAPK hyperactivation induced cytotoxicity. Furthermore, complete tumor regression was observed in an ERK2 overexpressing xenograft model. To identify mediators of MAPK hyperactivation- induced cell death, we conducted a large-scale pooled screen which showed that only shRNAs against BRAF and MAP2K1 rescued loss of cell viability. This suggested that no single downstream ERK2 effector was required, consistent with pleiotropic effects on multiple cellular stress pathways. Intriguingly, the detrimental effect of MAPK hyperactivation could be partially attributed to secreted factors, and more than 100 differentially secreted proteins were identified. The effect of ERK2 overexpression was highly context dependent, as RAS/RAF mutant but not RAS/RAF wildtype melanoma were sensitive to this perturbation. This vulnerability to MAPK hyperactivation raises the possibility of a novel therapeutic approach for RAS/RAF mutant cancers.
No associated publication
Sex, Specimen part, Disease, Cell line, Treatment
View SamplesWe established gene expression profiles of diagnostic bone marrow samples of monozygotic twins with acute lymphoblastic leukemia. We established technical duplicates for each twin.
Prenatal origin of separate evolution of leukemia in identical twins.
Sex, Specimen part, Disease, Disease stage
View SamplesDeficiency of the micronutrient zinc is a widespread condition in agricultural soils, generating a negative impact on crop quality and yield. Nevertheless, there is insufficient knowledge on the regulatory and molecular mechanisms underlying the plant response to inadequate zinc nutrition.
Transcriptomic profiling of Arabidopsis gene expression in response to varying micronutrient zinc supply.
Age, Specimen part
View SamplesGene expression profiles of paired normal adjacent mucosa and tumor samples from 98 individuals and 50 healthy colon mucosae, were obtained through Affymetrix Human Genome U219 Arrays. This dataset is in the context of the COLONOMICS project and to query additional information you can visit the project website www.colonomics.org.
Discovery and validation of new potential biomarkers for early detection of colon cancer.
Sex, Age, Disease, Subject
View SamplesApproximately one third of acute myeloid leukemias (AMLs) are characterized by aberrant cytoplasmic localization of Nucleophosmin (NPMc+ AML), consequent to mutations in the NPM putative nucleolar localization signal. These events are mutually exclusive with the major AML-associated chromosomal rearrangements, and are frequently associated with normal karyotype, Fms-like tyrosine kinase (FLT3) mutations and multilineage involvement. We report the gene expression profiles of 78 de novo AMLs (72 with normal karyotype; 6 with non-major chromosomal abnormalities) that were characterized for the subcellular localization and mutation status of NPM. Unsupervised clustering clearly separated NPMc+ from NPMc- AMLs, regardless of the presence of FLT3 mutations or non-major chromosomal rearrangements, supporting the concept that NPMc+ AML represents a distinct entity. The molecular signature of NPMc+ AML includes up-regulation of several genes putatively involved in the maintenance of a stem cell phenotype, suggesting that NPMc+ AML may derive from a multipotent hematopoietic progenitor.
Acute myeloid leukemia bearing cytoplasmic nucleophosmin (NPMc+ AML) shows a distinct gene expression profile characterized by up-regulation of genes involved in stem-cell maintenance.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
AML1/ETO oncoprotein is directed to AML1 binding regions and co-localizes with AML1 and HEB on its targets.
No sample metadata fields
View SamplesPRDM5 is a recently identified member of the PRDM family of proteins, which functions as a transcriptional repressor by recruiting histone methyltransferase G9A to DNA, and behaves as a putative tumor suppressor in different types of cancer.
The tumor suppressor PRDM5 regulates Wnt signaling at early stages of zebrafish development.
No sample metadata fields
View SamplesThe t(12;21) translocation is the most common genetic rearrangement in childhood acute lymphoblastic leukemia (ALL) and gives rise to the TEL-AML1 fusion gene, which functions as a transcription factor.
The TEL-AML1 fusion protein of acute lymphoblastic leukemia modulates IRF3 activity during early B-cell differentiation.
Cell line, Treatment
View Samples