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GSE84043
Homo sapiens
25 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genomic hallmarks of localized, non-indolent prostate cancer.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries. Local hypermutation events were frequent, and correlated with specific genomic profiles. Numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberrations outperformed well-described prognostic biomarkers. We suggest that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates.
Publication Title
Genomic hallmarks of localized, non-indolent prostate cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Herein we describe a molecular portrait of potentially curable, Gleason 7 and intermediate risk prostate cancer based on genome-wide CNV profiles of 96 patients, and subsequent whole-genome sequencing of 28 tumours from 10 patients, using DNA quantities that are achievable in diagnostic biopsies (50 ng). We show that Gleason 7 cancer is highly heterogeneous at the SNV, CNV, and intra-chromosomal translocation levels, and is characterized by a very low number of recurrent SNVs but significant structural variation. We identified a novel recurrent MYCL1 amplification, which was strongly associated with TP53 deletion and prognostic for biochemical recurrence in this cohort. Moreover, we identified clear evidence of divergent tumour evolution in multi focal cancer and, in 2/5 cases evaluated, multiple tumours of independent clonal origin. Taken together, these data represent the first systematic evaluation of the differential genomics of potentially curable prostate cancer, and strongly suggest that a more robust understanding of the relationship between genetic heterogeneity and clinical outcomes is required to effectively develop biomarkers of prognosis based on tumour genomics.
Publication Title
Spatial genomic heterogeneity within localized, multifocal prostate cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We wanted to test the role of mammalian E proteins E2A and HEB in the development of T cells.
Publication Title
An essential role for the transcription factor HEB in thymocyte survival, Tcra rearrangement and the development of natural killer T cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
CD8+ T cells play a crucial role in the clearance of intracellular pathogens through the generation of cytotoxic effector cells that eliminate infected cells and long-lived memory cells that provide enhanced protection against reinfection. We have previously shown that the inhibitor of E protein transcription factors, Id2, is necessary for accumulation of effector and memory CD8+ T cells during infection. Here we show that CD8+ T cells lacking Id2 did not generate a robust terminally-differentiated KLRG1hi effector population, but displayed a cell-surface phenotype and cytokine profile consistent with memory precursors, raising the question as to whether loss of Id2 impairs the differentiation and/or survival of effector-memory cells. We found that deletion of Bim rescued Id2-deficient CD8+ cell survival during infection. However, the dramatic reduction in KLRG1hi cells caused by loss of Id2 remained in the absence of Bim, such that Id2/Bim double-deficient cells form an exclusively KLRG1loCD127hi memory precursor population. Thus we describe a role for Id2 in both the survival and differentation of normal CD8+ effector and memory populations.
Publication Title
Id2 influences differentiation of killer cell lectin-like receptor G1(hi) short-lived CD8+ effector T cells.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 43 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Microarray analysis of parity induced gene expression changes in the mammary glands of four strains of rats to identify a common gene signature associated with protection against methylnitrosourea induced mammary tumorigenesis.
Publication Title
Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
To test whether SVD regression is sufficiently sensitive to detect activation of a secondary, endogenous pathway as it occurs following ectopic manipulation of a strong primary pathway by focusing on the relationship between the Ras and TGF signaling pathways.
Publication Title
Singular value decomposition-based regression identifies activation of endogenous signaling pathways in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
During an immune response, CD8 T cells fall along a gradient of memory potential, but the regulators of these fate decsisions are not well understood. We utlized Id3-GFP and Id2-YFP reporter mice to elucidate the role of Id3 and Id2 during early CD8 T cell differentiation by gene expression.
Publication Title
The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets.
Sample Metadata Fields
Sex, Specimen part
View Samples