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GSE60990
Homo sapiens
12 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Activating mutations of G protein alpha subunits (Ga) occur in 4-5% of all human cancers1 but oncogenic alterations in beta subunits (Gb) have not been defined. Here we demonstrate that recurrent mutations in the Gb proteins GNB1 and GNB2 confer cytokine-independent growth and activate canonical G protein signaling. Multiple mutations in GNB1 affect the protein interface that binds Ga subunits as well as downstream effectors, and disrupt Ga-Gbg interactions. Different mutations in Gb proteins clustered to some extent based on lineage; for example, all eleven GNB1 K57 mutations were in myeloid neoplasms while 6 of 7 GNB1 I80 mutations were in B cell neoplasms. Expression of patient-derived GNB1 alleles in Cdkn2a-deficient bone marrow followed by transplantation resulted in either myeloid or B cell malignancies. In vivo treatment with the dual PI3K/mTOR inhibitor BEZ235 suppressed GNB1-induced signaling and markedly increased survival. In several human tumors, GNB1 mutations co-occurred with oncogenic kinase alterations, including BCR/ABL, JAK2 V617F and BRAF V600K. Co-expression of patient-derived GNB1 alleles with these mutant kinases resulted in inhibitor resistance in each context. Thus, GNB1 and GNB2 mutations confer transformed and resistance phenotypes across a range of human tumors and may be targetable with inhibitors of G protein signaling.
Publication Title
Mutations in G protein β subunits promote transformation and kinase inhibitor resistance.
Sample Metadata Fields
Cell line, Time
View Samples- Danio rerio
- 43 Downloadable Samples
IlluminaHiSeq2000
Description
microRNAs (miRNAs) are typically generated as ~22-nucleotide double-stranded RNAs via processing of precursor hairpins by the RNase III enzyme Dicer, after which they are loaded into Argonaute (Ago) proteins to form RNA-induced silencing complex (RISC). However, the biogenesis of miR-451, an erythropoietic miRNA conserved in vertebrates, does not require Dicer processing. Instead, the short pre-miR-451 precursor hairpin is directly loaded into Ago, followed by cleavage of the 3'' arm and trimming of the 3'' end to the mature length by PARN. Here we show the in vivo activity of miR-430 Ago2-hairpin, a canonical microRNA engineered to fit the structure of miR-451 and hence become Ago2-dependent. Moreover, we test a modified miR-430 Ago2-haipin with 3x phoshorothioate bonds that impairs trimmng. Surprisingly, our data show that trimming of Ago-cleaved pre-miRNAs is not essential for target silencing, indicating that RISC is functional with miRNAs longer than 22-nucleotides. Overall design: Rescue of MZdicer zebrafish mutant with the injection of trimmable and nontrimmable miR-430 Ago2 hairpins: Transcriptome of wild type, MZdicer mutant, and MZdicer mutant micoinjected with miR-430 duplex, miR-430 (Ago2-haripin), miR-430 (Ago2-haripin 3xPhosphorothioate)
Publication Title
Poly(A)-specific ribonuclease mediates 3'-end trimming of Argonaute2-cleaved precursor microRNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- NextSeq 500
Description
In this manuscript, we described male-biased mutations in chrX genes in cancer. In this RNA-seq experiment we tested the transcriptional consequences of shRNA knockdown of one of those genes, CNKSR2 Overall design: Murine NIH 3T3 cells were infected with and selected for expression of lentiviruses expressing shRNAs targeting Cnksr2 (2 independent shRNA sequences) or a control shRNA (targeting RFP, a gene not present in these cells). Each was performed in biological triplicate independent cultures for n=9 total samples
Publication Title
Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex bias.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Affymetrix U133 Plus 2.0 arrays were hybridized with varying amounts of starting material to determine whether different measurements of gene expression were observed.
Publication Title
Identical probes on different high-density oligonucleotide microarrays can produce different measurements of gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Stratagene universal human RNA hybridized to both U133 Plus 2.0 and U133 A arrays.
Publication Title
Identical probes on different high-density oligonucleotide microarrays can produce different measurements of gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 119 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
DS-ALL is a highly heterogeneous disease with predominance of an aberrant exp. of CRLF2 cooperating with mutated JAK2
Publication Title
Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Earlier studies had shown that side population cells isolated from established non-small cell lung cancer (NSCLC) cell lines exhibit cancer stem cell properties. Microarray data from side population (SP) and main population (MP) cells isolated from 4 NSCLC lines (A549, H1650, H460, H1975) were used to examine gene expression profiles associated with stemness. Total RNA extracted from SP and MP samples were used to generate cRNA targets, which were hybridized to Human Genome U133 Plus 2.0 probe arrays. Raw data was processed and the mean center expression level for each gene was determined.
Publication Title
A novel five gene signature derived from stem-like side population cells predicts overall and recurrence-free survival in NSCLC.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CD24, or heat stable antigen, is a cell surface sialoglycoprotein expressed on immature cells that disappears after the cells have reached their final differentiation stage. CD24 may be important in human embryonic kidney epithelial cell differentiation. In mice, CD24 expression is up-regulated in the early metanephros and localized to developing epithelial structures but the role and expression of CD24 in the developing human kidney has not been well described. In normal human fetal kidneys from 8 to 38 weeks gestation, CD24 expression was up-regulated and restricted to the early epithelial aggregates of the metanephric blastema and to the committed proliferating tubular epithelia of the S-shape nephron; however individual CD24+ cells were identified in the interstitium of later gestation and postnatal kidneys. In freshly isolated cells, FACS analysis demonstrated distinct CD24+ and CD24+133+ cell populations, constituting up to 16% and 14% respectively of the total cells analyzed. Isolated and expanded CD24+ clones displayed features of an epithelial progenitor cell line. Early fetal urinary tract obstruction resulted in an upregulation of CD24 expression, both in developing epithelial structures of early gestation kidneys and in the cells of the injured tubular epithelium of the later gestation kidneys. These results highlight the cell specific expression of CD24 in the developing human kidney and dysregulation in fetal urinary tract obstruction.
Publication Title
Ontogeny of CD24 in the human kidney.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
OT-1 Transgenic CD8 T-cells were isolated from spleens of WT, PKC theta KO, and p50 cRel DKO mice. The T-cells were either cultured with non-pulsed DC (WT only and signified as "WT - UN") or with BMDCs pulsed with the OVA peptide SIINFEKL (N4) (WT, PKC theta KO, and p50 cRel DKO and signified as 'genotype - N4') at a ratio of 1:10 (DC:T-cell) for 18 hours. DCs then were depleted from the culture and RNA was made from the T-cells to measure gene expression at the early / late stage of T-cell activation
Publication Title
NF-κB is crucial in proximal T-cell signaling for calcium influx and NFAT activation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Illumina HiSeq 2000
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation.
Sample Metadata Fields
Specimen part
View Samples