Dataset Information

Microarray analysis of B-cell lymphoma cell lines with the t(14;18).

ABSTRACT: The t(14;18) is the most common genetic alteration in follicular lymphoma, and is detectable in a subset of diffuse large B-cell lymphomas (DLBCL), resulting in over-expression of the anti-apoptotic protein BCL-2. Although the t(14;18)-induced over-expression of BCL-2 is an important step in lymphomagenesis, this aberration alone is not sufficient to produce malignant lymphoma. Further analysis of these tumors is needed to identify additional genes that might be involved in the genesis of follicular lymphoma and progression to DLBCL. To address this issue, we analyzed the gene expression profiles of four t(14;18)-positive cell lines and two t(11;14)-positive mantle-cell lymphoma cell lines using cDNA microarrays containing 4364 genes, and compared them to the genetic profile of phenotypically purified B-cells obtained from hyperplastic tonsils. A total of 137 genes were differentially expressed by approximately twofold or more in the t(14;18) cell lines relative to tonsillar B-cells. 68 genes were up-regulated, 69 genes were down-regulated, and approximately 20% of the differentially regulated genes had no known function. The up-regulated genes included a number of genes involved in the promotion of cellular proliferation and survival, as well as cell metabolism. Down-regulated genes included mediators of cell adhesion and negative regulators of cell activation and growth. Hierarchical clustering analysis separated the t(14;18) and mantle-cell lines into distinct groups based on their gene expression profiles. We confirmed the differential expression of approximately 80% of selected up- and down-regulated genes identified by microarray analysis by quantitative real-time fluorescence reverse transcriptase polymerase chain reaction (RT-PCR) analysis and/or immunoblotting. This study demonstrates the utility of cDNA microarray analysis for the assessment of global transcriptional changes that characterize t(14;18)-positive cell lines, and also for the identification of novel genes that could potentially contribute to the genesis and progression of non-Hodgkin's lymphomas with this translocation.

SUBMITTER: Robetorye RS

PROVIDER: S-EPMC1906980 | biostudies-literature | 2002 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Microarray analysis of B-cell lymphoma cell lines with the t(14;18).

Robetorye Ryan S RS Bohling Sandra D SD Morgan John W JW Fillmore G Chris GC Lim Megan S MS Elenitoba-Johnson Kojo S J KS

The Journal of molecular diagnostics : JMD 20020801 3

The t(14;18) is the most common genetic alteration in follicular lymphoma, and is detectable in a subset of diffuse large B-cell lymphomas (DLBCL), resulting in over-expression of the anti-apoptotic protein BCL-2. Although the t(14;18)-induced over-expression of BCL-2 is an important step in lymphomagenesis, this aberration alone is not sufficient to produce malignant lymphoma. Further analysis of these tumors is needed to identify additional genes that might be involved in the genesis of follic ...[more]

PMID: 12169673

Similar Datasets

Project description:Several studies have demonstrated that metformin (MTF) acts with variable efficiency as an anticancer agent. The pleiotropic anticancer effects of MTF on cancer cells have not been fully explored yet. By interrogating the Gene Expression Omnibus (GEO) for microarray expression data, we identified eight eligible submissions, representing five different studies, that employed various conditions including different cell lines, MTF concentrations, treatment durations, and cellular components. A compilation of the data sets of 13 different conditions contained 443 repeatedly up- and 387 repeatedly down-regulated genes; the majority of these 830 differentially expressed genes (DEGs) were associated with higher MTF concentrations and longer MTF treatment. The most frequently upregulated genes include DNA damage inducible transcript 4 (DDIT4), chromodomain helicase DNA binding protein 2 (CHD2), endoplasmic reticulum to nucleus signaling 1 (ERN1), and growth differentiation factor 15 (GDF15). The most commonly downregulated genes include arrestin domain containing 4 (ARRDC4), and thioredoxin interacting protein (TXNIP). The most significantly (p-value < 0.05, Fisher's exact test) overrepresented protein class was entitled, nucleic acid binding. Cholesterol biosynthesis and other metabolic pathways were specifically affected by downregulated pathway molecules. In addition, cell cycle pathways were significantly related to the data set. Generated networks were significantly related to, e.g., carbohydrate and lipid metabolism, cancer, cell cycle, and DNA replication, recombination, and repair. A second compilation comprised genes that were at least under one condition up- and in at least another condition down-regulated. Herein, the most frequently deregulated genes include nuclear paraspeckle assembly transcript 1 (NEAT1) and insulin induced gene 1 (INSIG1). The most significantly overrepresented protein classes in this compilation were entitled, nucleic acid binding, ubiquitin-protein ligase, and mRNA processing factor. In conclusion, this study provides a comprehensive list of deregulated genes and biofunctions related to in vitro MTF application and individual responses to different conditions. Biofunctions affected by MTF include, e.g., cholesterol synthesis and other metabolic pathways, cell cycle, and DNA replication, recombination, and repair. These findings can assist in defining the conditions in which MTF exerts additive or synergistic effects in cancer treatment.

Dataset Information

Microarray analysis of B-cell lymphoma cell lines with the t(14;18).

Publications

Microarray analysis of B-cell lymphoma cell lines with the t(14;18).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets