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SRP076879
Homo sapiens
16 Downloadable Samples
Illumina HiSeq 2000
Description
The combination of JQ1 and Vemurafenib acted synergistically in BRAF-mutant cell lines, resulting in marked apoptosis in vitro, with up-regulation of pro-apoptotic proteins. In vivo, combination treatment suppressed tumor growth and significantly improved survival compared to either drug alone. RNA sequencing of tumor tissues revealed almost four thousand genes that were uniquely modulated by the combination, with several anti-apoptotic genes significantly down-regulated. Overall design: 16 samples analyzed from 8 mice (each mouse was bearing two tumors, one on each flank) in 4 treatment groups (control, vemurafenib alone, JQ1 alone, JQ1+vemurafenib)
Publication Title
BET and BRAF inhibitors act synergistically against BRAF-mutant melanoma.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HiSeq 2000
Description
Constitutive Wnt activation upon loss of Adenoma polyposis coli (APC) acts as main driver of colorectal cancers (CRC). Targeting Wnt signaling has proven difficult because the pathway is crucial for homeostasis and stem cell renewal. To distinguish oncogenic from physiologic Wnt activity, we have performed comprehensive transcriptome and proteome profiling in human colon organoids. Culture in the presence or absence of exogenous ligand allowed us to discriminate receptor-mediated signaling from the effects of CRISPR/Cas9 induced APC loss. We could catalogue two non-overlapping molecular signatures that were stable at distinct levels of stimulation. Newly identified markers for normal colon stem/progenitor cells and adenomas were validated by immunohistochemistry and flow cytometry. We found that oncogenic Wnt signals are associated with good prognosis in tumors of the consensus molecular subtype 2 (CMS2). In contrast, receptor-mediated signaling was linked to CMS4 tumors and poor prognosis. Together, our data represent a valuable resource for biomarkers that allow more precise stratification of Wnt responses in CRC. Overall design: Culturing normal and CRISPR/Cas9 engineered APC mutant isogenic organoid lines in the presence or absence of Wnt-stimulation, followed by transcriptome and proteome profiling allowed for the stratification of physiologic and oncogenic Wnt responses.
Publication Title
Human colon organoids reveal distinct physiologic and oncogenic Wnt responses.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Constitutive Wnt activation upon loss of Adenoma polyposis coli (APC) acts as main driver of colorectal cancers (CRC). Targeting Wnt signaling has proven difficult because the pathway is crucial for homeostasis and stem cell renewal. To distinguish oncogenic from physiologic Wnt activity, we have performed comprehensive transcriptome and proteome profiling in human colon organoids. Culture in the presence or absence of exogenous ligand allowed us to discriminate receptor-mediated signaling from the effects of CRISPR/Cas9 induced APC loss. We could catalogue two non-overlapping molecular signatures that were stable at distinct levels of stimulation. Newly identified markers for normal colon stem/progenitor cells and adenomas were validated by immunohistochemistry and flow cytometry. We found that oncogenic Wnt signals are associated with good prognosis in tumors of the consensus molecular subtype 2 (CMS2). In contrast, receptor-mediated signaling was linked to CMS4 tumors and poor prognosis. Together, our data represent a valuable resource for biomarkers that allow more precise stratification of Wnt responses in CRC. Overall design: Culturing normal and CRISPR/Cas9 engineered APC mutant isogenic organoid lines in the presence or absence of Wnt-stimulation, followed by transcriptome and proteome profiling allowed for the stratification of physiologic and oncogenic Wnt responses.
Publication Title
Human colon organoids reveal distinct physiologic and oncogenic Wnt responses.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 1 Downloadable Sample
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Although remission rates for metastatic melanoma are generally very poor, some patients can survive for prolonged periods following metastasis. We used gene expression profiling, mitotic index (MI), and quantification of tumor infiltrating leukocytes (TILs) and CD3+ cells in metastatic lesions to search for a molecular basis for this observation and to develop improved methods for predicting patient survival. We identified a group of 266 genes associated with postrecurrence survival. Genes positively associated with survival were predominantly immune response related (e.g., ICOS, CD3d, ZAP70, TRAT1, TARP, GZMK, LCK, CD2, CXCL13, CCL19, CCR7, VCAM1) while genes negatively associated with survival were cell proliferation related (e.g., PDE4D, CDK2, GREF1, NUSAP1, SPC24).
Publication Title
Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
FBXW7 modulates stress response by post-translational modification of HSF1 HSF1 orchestrates the heat-shock response upon exposure to heat stress and activates a transcriptional program vital for cancer cells. Genes positively regulated by HSF1 show increeased expression during heat shock while their expression is reduced during recovery. Genes negatively regulated by HSF1 show the opposite pattern. In this study we utilized the HCT116 FBXW7 KO colon cell line and its wild type counterpart to monitor gene expression changes during heat shock (42oC, 1 hour) and recovery (37oC for 2 hours post heat shock) using RNA sequencing. These results revealed that the heat-shock response pathway is prolonged in cells deficient for FBXW7. Overall design: Whole RNA was extracted from 1 million HCT116 WT or FBXW7KO cells using the RNAeasy kit (Qiagen) according to the manufacturer’s protocol. Poly-A+ (magnetic oligodT-containing beads (Invitrogen)) or Ribominus RNA was used for library preparation. cDNA preparation and strand-specific library construction was performed using the dUTP method. Libraries were sequenced on the Illumina HiSeq 2000 using 50bp single-read method. Differential gene expression analysis was performed for each matched recovery versus heat-shock pairs, separately in each biological replicate and cell line (WT or KO). Two types of comparisons were tested: (a) WT recovery vs WT heat shock, (b) FBXW7 KO recovery vs heat shock.
Publication Title
FBXW7 modulates cellular stress response and metastatic potential through HSF1 post-translational modification.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HiSeq 4000
Description
We report RNAseq data from subsequent passages of five organoid cultures. Overall design: RNA extracted from subsequent PDO passages was subjected to RNAseq.
Publication Title
Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.
Sample Metadata Fields
Disease, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The two most common melanoma histopathologic subtypes, superficial spreading (SSM) and nodular melanoma (NM), are believed to represent sequential phases of linear progression from radial to vertical growth. Studies suggest, however, that SSM and NM are biologically distinct. We utilized an integrative genomic approach to examine the possibility that SSM and NM are the result of independent pathways characterized by unique molecular alterations. Cell lines including SSM, NM, metastatic melanoma, and melanocyte controls were evaluated for copy number changes and differential mRNA expression using single nucleotide polymorphism array (SNP 6.0, Affymetrix) and gene array (U133A 2.0, Affymetrix). Data sets were integrated to identify copy number alterations that correlated with gene expression, and array results were validated using immunohistochemistry on human tissue microarrays (TMAs) and an external data set. The functional effect of genomic deletion was assessed by lentiviral overexpression. Integrative genomics revealed 8 genes in which NM/SSM-specific copy number alterations were correlated with NM/SSM differential gene expression (P<0.05, Spearmans rank). Pathways analysis of differentially expressed genes (N=114) showed enrichment for metabolic-related processes. SSM-specific genomic deletions (DIS3, MTAP, G3BP2, SEC23IP, USO1) were verified in an expanded panel of cell lines, and forced overexpression of MTAP in SSM resulted in reduced cell growth. Metabolism-related gene ALDH7A1 was verified as overexpressed in NM using human TMAs.The identification of recurrent genomic deletions in SSM not present in NM challenges the linear model of melanoma progression and supports the unique molecular classification of SSM and NM.
Publication Title
Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To metastasize, a tumor cell must acquire abilities such as the capacity to colonize new tissue and evade immune surveillance. Recent evidence suggests that microRNAs can promote the evolution of malignant behaviors by regulating multiple targets simultaneously. We performed a microRNA analysis of human melanoma, an aggressively invasive cancer, and found that miR-30b/30d upregulation correlates with stage, metastatic potential of primary tumors, shorter time to recurrence and reduced overall survival. Ectopic expression of miR-30b/30d promoted the metastatic behavior of melanoma cells by directly targeting the GalNAc transferase GALNT7, resulted in increased synthesis of the immunosuppressive cytokine IL-10, and reduced immune cell activation and recruitment. These data point to a key role of miR-30b/30d and GalNAc transferases in metastasis, by simultaneously promoting cellular invasion and immune suppression.
Publication Title
miR-30b/30d regulation of GalNAc transferases enhances invasion and immunosuppression during metastasis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2000, Illumina Genome Analyzer IIx, Illumina HiSeq 1000, Illumina Genome Analyzer II
Description
We report cell type specific Nova HITS-CLIP using BAC-transgenic lines expressing GFP-Nova under the motor neuron specific choline acetyltransferase (Chat) promoter. By comparing transcriptome wide Nova binding map in motor neurons and that in the whole spinal cord, we identified differential Nova binding sites in motor neurons, which correlate with motor neuron specific RNA processing. Overall design: 14 total samples were analyzed. For HITS-CLIP, 4 biological replicates were performed for each BAC-transgenic line, as well as the whole spinal cord. For RNA-seq, 2 biological repliates were performed on the whole spinal cord.
Publication Title
Cell type-specific CLIP reveals that NOVA regulates cytoskeleton interactions in motoneurons.
Sample Metadata Fields
No sample metadata fields
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