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SRP076990
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2500
Description
Half of prostate cancers are caused by a gene-fusion that enables androgens to drive expression of the normally silent ETS transcription factor ERG in luminal prostate cells1-4. Recent prostate cancer genomic landscape studies5-10 have reported rare but recurrent point mutations in the ETS repressor ERF11. Here we show these ERF mutations cause decreased protein stability and ERF mutant tumours are mostly exclusive from those with ERG fusions. ERF loss recapitulates the morphologic and phenotypic features of ERG gain in primary mouse prostate tissue, including expansion of the androgen receptor (AR) transcriptional repertoire, and ERF has tumour suppressor activity in the same genetic background of PTEN loss that yields oncogenic activity by ERG. Furthermore, in a human prostate cancer model of ERG gain and wild-type ERF, ChIP-seq studies indicate that ERG inhibits the ability of ERF to bind DNA at consensus ETS sites. Consistent with a competition model, ERF loss rescues ERG-positive prostate cancer cells from ERG dependency. Collectively, these data provide evidence that the oncogenicity of ERG is mediated, in part, by displacement of ERF and raise the larger question of whether other gain-of-function oncogenic transcription factors might also inactivate endogenous tumour suppressors. Overall design: Murine Pten+/+ prostates were infected with shNT or shErf lentivirus, selected with antibiotics and 2 rounds of FACS. For each condition, 2 sets of equal numbers of cells were plated and then processed for RNA extraction and RNA-seq independently.
Publication Title
ERF mutations reveal a balance of ETS factors controlling prostate oncogenesis.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 1000
Description
Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS transcriptome profiling (RNA-seq) from whole eye, after removal of the lens and cornea from 1-2 month old miR-211-/- mice and compare it with wt mice Methods: Whole eye (after removal of the lens and cornea) mRNA profiles of 1-2 month old wild-type (WT) and neural miR-211-/-mice were generated by deep sequencing, in multiple biological replicates, five for WT and six for miR-211-/- animals, using Illumina GAIIx. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays RNA-Seq libraries were prepared from whole eye, after removal of the lens and cornea from miR-211-/- mice. Results: Each library was sequenced using 100 bp paired-end sequencing on the Illumina HiSeq 1000 system. Gene abundances from RNA-Seq data were quantified using RSEM45. Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the mouse genome. This approach yielded read count values for a total of 38253 mouse genes annotated in GenCode. We only considered genes that had at least 1 count per million in at least five out of 11 samples as expressed, yielding a total of 15590 genes. Next we performed differential gene expression analysis to determine the transcriptional effects of miR-211 deletion. This analysis yielded a total of 63 genes that were differentially expressed with a False Discovery Rate (FDR) <0.1 (Fig. 4). Of these, the expression levels of 61 genes were significantly decreased upon miR-211 deletion, while only 2 genes were upregulated. Conclusions: Our study represents the first detailed analysis of whole eye transcriptomes, with biologic replicates, generated by RNA-seq technology on miR-211-/-. Overall design: Whole eye (after removal of the lens and cornea) mRNA profiles of 1-2 month old wild-type (WT) and neural miR-211-/-mice were generated by deep sequencing, in multiple biological replicates, five for WT and six for miR-211-/- animals, using Illumina GAIIx.
Publication Title
MiR-211 is essential for adult cone photoreceptor maintenance and visual function.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 188 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P=.01). High expression of cytotoxic genesignaturewithin the TBX21 subgroup also showed poor clinical outcome (P=.05). InAITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P=.004).
Publication Title
Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 147 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Molecular signatures to improve diagnosis in PTCL and prognostication in angioimmunoblastic T-cell lymphoma (AITL). Gene expression profiling of PTCL patient samples was performed to investigate whether molecular signatures can be used to identify distinct entities of PTCL.
Publication Title
Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 44 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
NK-cell lymphoma shares strikingly similar molecular features with a distinct subset of gamma-delta T-cell lymphoma. Gene expression profiling of NK-cell lymphoma patient samples was performed to investigate whether molecular signatures can be used to identify entities of peripheral T-cell lymphoma (PTCL) with NK-cell-like features.
Publication Title
Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
RANK-positive and RANK-negative luminal progenitor cells were isolated by FACS from histologically normal human breast tissue from wild-type human donors. RNA-seq gene expression profiling was used to find differentially expressed genes between the RANK-positive and RANK-negative cell populations. Overall design: Cells were isolated from 4 human patients. A paired analysis was used to compare RANK-positive and RANK-negative cells within patients.
Publication Title
RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HiSeq 2000
Description
CD11c+ B cells (IgD+ and IgD-) are pathogenic B cells expanded in autoimmune disease. The purpose of this study is to identify the pathways unique to IgD+ CD11c B cells and IgD- CD11c B cells. Overall design: B cell subsets were isolated from peripheral blood and RNA sequencing was performed with Hiseq 2000 platform
Publication Title
IL-21 drives expansion and plasma cell differentiation of autoreactive CD11c<sup>hi</sup>T-bet<sup>+</sup> B cells in SLE.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
BRCA1, a well-known breast and ovarian cancer susceptibility gene with multiple interacting partners, is predicted to have diverse biological functions. However, to date its only well-established role is in the repair of damaged DNA and cell cycle regulation. In this regard, the etiopathological study of low penetrant variants of BRCA1 provides an opportunity to uncover its other physiologically important functions. Using this rationale, we studied the R1699Q variant of BRCA1, a potentially moderate risk variant, and found that it does not impair DNA damage repair but abrogates the repression of miR-155, a bona fide oncomir. We further show that in the absence of functional BRCA1, miR-155 is up-regulated in BRCA1-deficient mouse mammary epithelial cells, human and mouse BRCA1-deficienct breast tumor cell lines as well as tumors. Mechanistically, we found that BRCA1 represses miR-155 expression via its association with HDAC2, which deacetylates H2A and H3 on the miR-155 promoter. Finally, we show that over-expression of miR-155 accelerates whereas the knockdown of miR-155 attenuates the growth of tumor cell lines in vivo. Taken together, our findings demonstrate a new mode of tumor suppression by BRCA1 and reveal miR-155 as a potential therapeutic target for BRCA1-deficient tumors.
Publication Title
Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We examined the functional significance of the R1699Q variant of human BRCA1 gene using a mouse ES cell-based assay.
Publication Title
Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 47 Downloadable Samples
- IlluminaHiSeq2000
Description
In this study we aimed to assess technical variability associated with globin depletion in addition to assessing general technical variability in RNA-Seq from whole blood derived samples. We compared technical and biological replicates having undergone globin depletion or not and found that globin depletion removed approximately 80% of globin transcripts, improved the correlation of technical replicates, allowed for reliable detection of thousands of additional transcripts and generally increased transcript abundance measures. Overall design: Peripheral whole blood transcriptome assessed by RNA-Seq on Illumina HiSeq 2000 in 6 healthy individuals and 6 pooled samples, either globin depleted or not.
Publication Title
Variation in RNA-Seq transcriptome profiles of peripheral whole blood from healthy individuals with and without globin depletion.
Sample Metadata Fields
No sample metadata fields
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