Immune cell-specific expression is one indication of the importance of a gene's role in the immune response.
Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients.
Sex, Age, Specimen part, Disease
View SamplesProfiling project of CRC patient material collected in the Academic Medical Center (AMC) in Amsterdam, The Netherlands. We focused on a set of 90 AJCC stage II patients that underwent intentionally curative surgery in the years 1997-2006 (AMC-AJCCII-90). Extensive medical records are kept from these patients and long-term clinical follow-up is available for the large majority. Both paraffin-embedded as well as fresh frozen tissue is available from all these patients for analysis.
Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients.
Sex, Age, Specimen part, Disease
View SamplesPrimary colon CSC cultures were transduced with a Wnt responsive construct (TOP-GFP). 10% highest and lowest TOP-GFP cell fractions were FACS sorted and arrayed.
Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients.
Specimen part
View SamplesBackground: Acute myeloid leukemia (AML) is driven by somatic mutations and genomic rearrangements affecting >20 genes. Many of these are recent discoveries and how this molecular heterogeneity dictates AML pathophysiology and clinical outcome remains unclear. Methods: We sequenced 111 leukemia genes for driver mutations in 1540 AML patients with cytogenetic and clinical data. We modeled AMLs genomic structure, defining genetic interactions, patterns of temporal evolution and clinical correlations. Results: We identified 5,236 driver mutations involving 77 loci, including hotspot mutations in MYC. We found 1 driver mutation in 96% patients, and 2 in 85%. Gene mutations implicated in age related clonal hematopoiesis (DNMT3A, ASXL1, TET2) were the earliest in AML evolution, followed by highly specific and ordered patterns of co-mutation in chromatin, transcription and splicing regulators, NPM1 and signaling genes. The patterns of co-mutation compartmentalize AML into 12 discrete molecular classes, each presenting with distinct clinical manifestation. Amongst these, mutations in chromatin and spliceosome genes demarcate a molecularly heterogeneous subgroup enriched for older AML patients currently classified as intermediate risk and results in adverse prognosis. Two- and three-way genetic interactions often implicating rare genes/mutation-hotspots, markedly redefined clinical response and long-term curability, with the NPM1:DNMT3A:FLT3ITD genotype (6% patients) identifying poor prognosis disease, whereas within the same class NPM1:DNMT3A:NRASG12/13 (3%) associated with favorable outlooks. Conclusions: 79% of AML is molecularly classified in 12 genomic subgroups. These represent distinct molecular phylogenies, implicating complex genotypes. Delineation of higher-order genomic relationships, guide the development of personally tailored classification, prognostication and clinical protocols. Similar studies across cancer types are warranted.
Genomic Classification and Prognosis in Acute Myeloid Leukemia.
Specimen part, Disease
View SamplesWe used unsupervised hierarchical clustering to analyse expression in primary ovarian tumors and associated abdominal deposits. GeneGo pathway analysis of differentially expressed genes between primary tumors and deposits revealed 4 of the top 10 pathways related to cytoskeleton remodeling and cell adhesion.
LRP1B deletion in high-grade serous ovarian cancers is associated with acquired chemotherapy resistance to liposomal doxorubicin.
Sex, Specimen part, Subject
View SamplesIL-22 acts on epithelial cells and has been shown to induce tissue protective and wound healing responses in these cells. But it has recently been decribed that IL-22 exacerbates ileatis after infection with T. gondii.
Interleukin-22 induces interleukin-18 expression from epithelial cells during intestinal infection.
Specimen part, Time
View SamplesThe human bone marrow (BM) gives rise to all distinct blood cell lineages, including CD1c+ and CD141+ myeloid dendritic cells (DC) and monocytes. These cell subsets are also present in peripheral blood (PB) and lymphoid tissues. However, the difference between the BM and PB compartment in terms of differentiation state and immunological role of DC is not yet known. The BM may represent both a site for development as well as a possible effector site and so far, little is known in this light with respect to different DC subsets. Using genome-wide transcriptional profiling we found clear differences between the BM and PB compartment and a location-dependent clustering for CD1c+ and CD141+ was demonstrated. DC subsets from BM clustered together and separate from the corresponding subsets from PB, which similarly formed a cluster. In BM, a common proliferating and immature differentiating state was observed for the two DC subsets, whereas DC from the PB showed a more immune-activated mature profile. In contrast, BM-derived slan+ non-classical monocytes were closely related to their PB counterparts and not to DC subsets, implying a homogenous prolife irrespective of anatomical localization. Additional functional tests confirmed these transcriptional findings. DC-like functions were prominently exhibited by PB DC. They surpassed BM DC in maturation capacity, cytokine production and induction of CD4+ and CD8+ T cell proliferation. This first study on myeloid DC in healthy human BM offers new information on steady-state DC biology and could potentially serve as a starting point for further research on these immune cells in healthy conditions as well as in diseases.
Human Bone Marrow-Derived Myeloid Dendritic Cells Show an Immature Transcriptional and Functional Profile Compared to Their Peripheral Blood Counterparts and Separate from Slan+ Non-Classical Monocytes.
Specimen part
View SamplesAbstract: Human 6-sulfo LacNac (slan)+ cells have been subject to a paradigm debate. They have previously been classified as a distinct dendritic cell (DC) subset. However, evidence has emerged that they may be more related to monocytes than to DC. To gain deeper insight into the functional specialization of slan+ cells, we have compared them with both conventional myeloid DC subsets (CD1c+ and CD141+) in human peripheral blood. Using genome-wide transcriptional profiling as well as extensive functional tests, we clearly show that slan+ cells form a distinct, non-DC-like, population. They cluster away from both DC subsets and their gene expression profile evidently suggests involvement in distinct inflammatory processes. An extensive comparison with existing genomic data sets also strongly confirmed the relationship of slan+ with the monocytic compartment rather than with DC. From a functional perspective, their ability to induce CD4+ and CD8+ T cell proliferation is relatively low. Combined with the finding that antigen presentation by MHC class II is at the top of under-represented pathways in slan+ cells, this points to a minimal role in directing adaptive T cell immunity. Rather, the higher expression of complement receptors on their cell surface, together with their high secretion of IL-1 and IL-6, imply a specific role in innate inflammatory processes, which is consistent with their recent identification as non-classical monocytes. This study extends our knowledge on DC/monocyte subset biology under steady state conditions and contributes to our understanding of their role in immune-mediated diseases and their potential use in immunotherapeutic strategies.
Transcriptional profiling reveals functional dichotomy between human slan<sup>+</sup> non-classical monocytes and myeloid dendritic cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer.
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