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Homo sapiens
18 Downloadable Samples
Illumina HiSeq 4000
Description
The 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.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Disease, Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
We established gene expression profiles of diagnostic bone marrow samples of monozygotic twins with acute lymphoblastic leukemia. We established technical duplicates for each twin.
Publication Title
Prenatal origin of separate evolution of leukemia in identical twins.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 121 Downloadable Samples
Description
To facilitate preclinical translational science, this cohort of patient-derived xenograft (PDX) models of leukemia and lymphoma has undergone molecular characterization with whole transcriptome sequencing, targeted exon sequencing of genes recurrently altered in leukemia and lymphoma, and other approaches. Here we provide the whole transcriptome sequencing data for these PDX models. Related molecular data and de-identified clinical information can be obtained at http://www.proxe.org.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 76 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
MAP3K11 overexpression in tumors leads to weight loss in the host
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Post-chemotherapy relapse presents a major unmet medical need in AML where treatment options are limited. We used gene expression profile from 32 AML cell lines to characterize expression difference between responder and non-responders to PIM inhibitors. Our results highlight the importance of STAT5 and MYC in rendering cancer cells sensitive to PIM inhibitors.
Publication Title
No associated publication
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 27 Downloadable Samples
Description
Total RNA sequencing data from primary colorectal tumors, liver metastasis and patient derived xenographs. Persistence of Fusobacterium and co-occuring anaerobic bacteria in human colorectal cancer.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Identification of down-down target genes differentially regulated by the MECT1-MAML2 oncoprotein, as compared to two translocation gene partners, MAML2 and MECT1.
Publication Title
Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The aim of this experiment was to get a comparison of the signatures between a non-transformed cell (NIH3T3 + vector) and a transformed cell (NIH3T3 + Fbxo7). NIH3T3 cells become transformed after the stable integration of the Fbxo7 gene. Fbxo7 potentiates cyclin D/cdk6 activity.
Publication Title
Transforming activity of Fbxo7 is mediated specifically through regulation of cyclin D/cdk6.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- NextSeq 500
Description
No description.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment
View Samples
SRP097916- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
UCA1 is an oncogene in ovarian cancer (OC). UCA1 was knocked down in OC cell lines and RNA-sequencing performed to profile the target genes.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples