Project description:This SuperSeries is composed of the following subset Series: GSE24877: Differential Gene Expression and Clonal Selection during Cellular Transformation Induced by Adhesion Deprivation (A16 vs NA16) GSE24878: Differential Gene Expression and Clonal Selection during Cellular Transformation Induced by Adhesion Deprivation (A16 vs COLONY) GSE24879: Differential Gene Expression and Clonal Selection during Cellular Transformation Induced by Adhesion Deprivation (A16 vs. Tumor) Refer to individual Series
Project description:Cell substrate adhesion plays an important role in cellular transformation of rat fibroblast cell lines, however a few viable non-adherent fibroblast cells when placed in suspension for a time period of 16 h (NA16) showed varied phenotypic characteristics like colony and tumor formation In order to understand the molecular events associated with adhesion independent cell survival ability of NA16, whole genome profiling was performed using Affymetrix Rat 230_2 GeneChips Keywords: Expression profiling of a adhesion deprived transformed cell line F111 fibroblast cell lines were grown in adhesion (A16) and suspension (NA16) conditions for 16h. These suspension cells (NA16) were plated on soft agar for colony formation and also injected in nude mice subcutaneously for tumor formation. A16 samples were considered as the control ones. Total RNA isolated from the samples (A16, NA16, Colony and Tumor) was subjected for expression analysis using Affymetrix Rat 230.2 GeneChip System. The experiment was repeated biologically and technically twice.
Project description:Cell substrate adhesion plays an important role in cellular transformation of rat fibroblast cell lines, however a few viable non-adherent fibroblast cells when placed in suspension for a time period of 16 h (NA16) showed varied phenotypic characteristics like colony and tumor formation In order to understand the molecular events associated with adhesion independent cell survival ability of NA16, whole genome profiling was performed using Affymetrix Rat 230_2 GeneChips Keywords: Expression profiling of a adhesion deprived transformed cell line F111 fibroblast cell lines were grown in adhesion (A16) and suspension (NA16) conditions for 16h. These suspension cells (NA16) were plated on soft agar for colony formation and also injected in nude mice subcutaneously for tumor formation. A16 samples were considered as the control ones. Total RNA isolated from the samples (A16, NA16, Colony and Tumor) was subjected for expression analysis using Affymetrix Rat 230.2 GeneChip System. The experiment was repeated biologically and technically twice.
Project description:Cell substrate adhesion plays an important role in cellular transformation of rat fibroblast cell lines, however a few viable non-adherent fibroblast cells when placed in suspension for a time period of 16 h (NA16) showed varied phenotypic characteristics like colony and tumor formation In order to understand the molecular events associated with adhesion independent cell survival ability of NA16, whole genome profiling was performed using Affymetrix Rat 230_2 GeneChips Keywords: Expression profiling of a adhesion deprived transformed cell line F111 fibroblast cell lines were grown in adhesion (A16) and suspension (NA16) conditions for 16h. These suspension cells (NA16) were plated on soft agar for colony formation and also injected in nude mice subcutaneously for tumor formation. A16 samples were considered as the control ones. Total RNA isolated from the samples (A16, NA16, Colony and Tumor) was subjected for expression analysis using Affymetrix Rat 230.2 GeneChip System. The experiment was repeated biologically and technically twice.
Project description:Although information on the molecular pathogenesis of Waldenström’s Macroglobulinemia (WM) has greatly improved in recent years, the exact cellular origin and the mechanisms behind WM transformation from IgM MGUS remain undetermined. Here, we undertook an integrative phenotypic, molecular and genomic approach to study clonal B-cells from newly-diagnosed patients with IgM MGUS (n=22), smoldering (n=17), and symptomatic WM (n=10). Through principal-component-analysis of multidimensional flow cytometry data, we demonstrated overlapping phenotypic profiles between clonal B-cells from IgM MGUS, smoldering and symptomatic WM patients. Similarly, virtually no genes were significantly deregulated between FACS-sorted clonal B-cells from the three disease stages. Interestingly, while the transcriptome of the Waldenström’s clone was highly deregulated as compared to CD25-CD22+ normal B-cells, significantly less genes were differentially expressed and specific WM pathways down-regulated while comparing the transcriptome of the Waldenström’s clone vs. its normal phenotypic counterpart: CD25+CD22+dim B-cells. The frequency of specific copy number abnormalities [+4, del(6q23.3-6q25.3), +12, and +18q11-18q23] progressively increased from IgM MGUS and smoldering WM vs. symptomatic WM (18% vs. 20% and 73%, respectively; P =.008), suggesting a multistep transformation of clonal B-cells that albeit benign (i.e.: IgM MGUS and smoldering WM), already harbor the phenotypic and molecular signatures of the malignant Waldenström’s clone. Normal bone marrow CD25+ B-cells, Clonal B-Cells from IgM Monoclonal Gammopathy of Undetermined Significance, and Clonal B-Cells from Waldenström's Macroglobulinemia
Project description:Although information on the molecular pathogenesis of Waldenström’s Macroglobulinemia (WM) has greatly improved in recent years, the exact cellular origin and the mechanisms behind WM transformation from IgM MGUS remain undetermined. Here, we undertook an integrative phenotypic, molecular and genomic approach to study clonal B-cells from newly-diagnosed patients with IgM MGUS (n=22), smoldering (n=17), and symptomatic WM (n=10). Through principal-component-analysis of multidimensional flow cytometry data, we demonstrated overlapping phenotypic profiles between clonal B-cells from IgM MGUS, smoldering and symptomatic WM patients. Similarly, virtually no genes were significantly deregulated between FACS-sorted clonal B-cells from the three disease stages. Interestingly, while the transcriptome of the Waldenström’s clone was highly deregulated as compared to CD25-CD22+ normal B-cells, significantly less genes were differentially expressed and specific WM pathways down-regulated while comparing the transcriptome of the Waldenström’s clone vs. its normal phenotypic counterpart: CD25+CD22+dim B-cells. The frequency of specific copy number abnormalities [+4, del(6q23.3-6q25.3), +12, and +18q11-18q23] progressively increased from IgM MGUS and smoldering WM vs. symptomatic WM (18% vs. 20% and 73%, respectively; P =.008), suggesting a multistep transformation of clonal B-cells that albeit benign (i.e.: IgM MGUS and smoldering WM), already harbor the phenotypic and molecular signatures of the malignant Waldenström’s clone. Copy number analysis using the Affymetrix CytoScan 750K Array to study clonal B-cells from newly-diagnosed patients with IgM MGUS, smoldering, and symptomatic WM. Peripheral T-cells from paired and unpaired controls were also assessed.
Project description:Although information on the molecular pathogenesis of Waldenström’s Macroglobulinemia (WM) has greatly improved in recent years, the exact cellular origin and the mechanisms behind WM transformation from IgM MGUS remain undetermined. Here, we undertook an integrative phenotypic, molecular and genomic approach to study clonal B-cells from newly-diagnosed patients with IgM MGUS (n=22), smoldering (n=17), and symptomatic WM (n=10). Through principal-component-analysis of multidimensional flow cytometry data, we demonstrated overlapping phenotypic profiles between clonal B-cells from IgM MGUS, smoldering and symptomatic WM patients. Similarly, virtually no genes were significantly deregulated between FACS-sorted clonal B-cells from the three disease stages. Interestingly, while the transcriptome of the Waldenström’s clone was highly deregulated as compared to CD25-CD22+ normal B-cells, significantly less genes were differentially expressed and specific WM pathways down-regulated while comparing the transcriptome of the Waldenström’s clone vs. its normal phenotypic counterpart: CD25+CD22+dim B-cells. The frequency of specific copy number abnormalities [+4, del(6q23.3-6q25.3), +12, and +18q11-18q23] progressively increased from IgM MGUS and smoldering WM vs. symptomatic WM (18% vs. 20% and 73%, respectively; P =.008), suggesting a multistep transformation of clonal B-cells that albeit benign (i.e.: IgM MGUS and smoldering WM), already harbor the phenotypic and molecular signatures of the malignant Waldenström’s clone.