This SuperSeries is composed of the SubSeries listed below.
Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs.
Specimen part, Cell line
View SamplesBurkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34% of Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a new tumor suppressor gene.
Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs.
Specimen part, Cell line
View SamplesTwist1 variants including wildtype Twist1, a non-phosphorylatable mutant Twist1/S42A and a phospho-mimicking mutant Twist1/S42D were expressed in 4T1 cells in which the endogenous Twist1 was depleted.
Akt/PKB-mediated phosphorylation of Twist1 promotes tumor metastasis via mediating cross-talk between PI3K/Akt and TGF-β signaling axes.
Specimen part
View SamplesRANK-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.
RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers.
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View SamplesThis SuperSeries is composed of the SubSeries listed below. A subset of samples profiled in this analysis were also profiled in Series GSE68127, and GSE104066. Corresponding glomerular transcriptome data can be found under GEO ID: GSE108109.
Metabolic pathways and immunometabolism in rare kidney diseases.
Specimen part
View Samplessummary : Glomerular Transcriptome from European Renal cDNA Bank subjects and living donors. Samples included in this analysis have been previously analyzed using older CDF definitions and are included under previous GEO submissions - GSE47183 (chronic kidney disease samples), and GSE32591 (IgA nephropathy samples).
Metabolic pathways and immunometabolism in rare kidney diseases.
Specimen part, Disease
View Samplessummary : Tubulointerstitial transcriptome from ERCB subjects with chronic kidney disease and living donor biopsies. Samples included in this analysis have been previously analyzed using older CDF definitions and are included under previous GEO submissions - GSE47184 (chronic kidney disease samples), and GSE32591 (IgA nephropathy samples).
Metabolic pathways and immunometabolism in rare kidney diseases.
Specimen part, Disease
View SamplesTubulointerstitial transcriptome from human kidney biopsies in Neptune and ERCB. A number of samples profiled in this analysis were also profiled in Series GSE68127.
Metabolic pathways and immunometabolism in rare kidney diseases.
Specimen part
View SamplesGlomerular transcriptome from human kidney biopsies in Neptune and ERCB. A subset of samples profiled in this analysis were also profiled in Series GSE68127, and in GSE104066. Corresponding tubulointerstitial transcriptome data is submitted under GEO ID: GSE108113.
Metabolic pathways and immunometabolism in rare kidney diseases.
Specimen part
View SamplesBRCA1, 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.
Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155.
Specimen part
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