Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profiling of age-related EBV-positive B-cell lymphoproliferative disorders uncovers alterations in characteristic oncogenetic pathways: possible implications for pathogenesis

ABSTRACT: Comprehensive gene expression profiles of Epstein-Barr virus (EBV)-associated B cell neoplasm (clinical samples + cell lines)

ORGANISM(S): Homo sapiens

SUBMITTER: Kato Harumi

PROVIDER: E-MTAB-973 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression profiling of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways.

Kato Harumi H Karube Kennosuke K Yamamoto Kazuhito K Takizawa Jun J Tsuzuki Shinobu S Yatabe Yasushi Y Kanda Teru T Katayama Miyuki M Ozawa Yukiyasu Y Ishitsuka Kenji K Okamoto Masataka M Kinoshita Tomohiro T Ohshima Koichi K Nakamura Shigeo S Morishima Yasuo Y Seto Masao M

Cancer science 20140409 5

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly (EBV[+]DLBCL-E) is classified as a subtype of DLBCL. Until now, its molecular pathogenesis has remained unknown. To identify pathways characteristic of EBV(+)DLBCL-E, gene expression profiling of five EBV(+)DLBCL-E and seven EBV-negative DLBCL (EBV[-]DLBCL) cases was undertaken using human oligonucleotide microarray analysis. Gene set enrichment analysis and gene ontology analysis showed that gene sets of the ...[more]

PMID: 24581222

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Project description:Synthetic systems that use positive feedback have been developed to control human disease vectors and crop pests. The tTAV system, which has been deployed in several insect species, relies on a positive feedback circuit that can be inhibited via dietary tetracycline. Although insects carrying tTAV fail to survive until adulthood in the absence of tetracycline, the exact reason for its lethality, as well as the transcriptomic effects of an active positive feedback circuit, remain unknown. Understanding what factors contribute to the variance in tTAV-associated mortality is likely to inform the development of insect control systems. In the present study, the OXI513a tTAV feedback circuit was introduced and verified into D. melanogaster. The tight tetracycline regulation of the system affords a convenient method to conduct a strain-by-strain assessment of the tTAV system and determine the transcriptomic effect, if any, of a positive feedback circuit. Transcriptomic analysis of four independent D. melanogaster tTAV insertion lines, in both adults and larvae, was conducted to examine the transcriptomic influence of the tTAV system. The tTAV lines and non-tTAV control were maintained on TET-on media for 5 generations prior to commencing. Thirty flies, 15 male and 15 female, of the same age, from each of the strains were transferred to either TET-On or TET-Off media. Five days after transfer, adult flies were removed and 10 adult flies, 5 male & 5 female, were frozen at -80°C. Ten larvae from each of these matings were collected at the late second instar stage, the last life stage normally seen prior to lethality, and frozen at -80°C. Three biological replicates were produced for each combination of strain, life-stage, and media. RNA was prepared from frozen samples using Trizol and DNAse was treated using a PureLink RNA Mini Kit (Invitrogen). Microarray experiments employed Agilent Drosophila Gene Expression Microarrays 4x44K and were scanned on an Agilent G2505C scanner (Agilent Technologies). Data collection was divided into two separate experiments. A pilot experiment for strain 102D consisting of two life stages in two conditions each with three biological replicates – a total of 12 samples. The remaining four strains were run as a separate experiment with a total of 48 samples. For each experiment, sample chip position was randomized to avoid genotype- and treatment-specific batch effects.

Project description:We proposed that the frequency of EBV reactivation may be crucial for its pathogenic role and highly recurrent EBV reactivations exert a profound influence on genome instability. Recurrent reactivations were induced in the EBV-latently infected NPC cells (NA cells) by treating with 12-o-tetradecanoylphorbol-13-acetate (TPA) and sodium n-butyrate (SB) once per passage periodically. Genome-wild oligoarray-based comparative genomic hybridization (CGH) technology was applied to investigate the copy-number aberrations in response for different frequencies of EBV reactivation. The results showed that the NR15 cells, NA cells with the highest frequency (15 times) of reactivation, exhibit extensive genomic copy-number alterations (CNAs) mostly involving chromosome 3p, 3q, 8p, 8q, 9p and 9q, whereas limited number of CNAs were observed both in NR1 cells where only the initial reactivation take place and NP15 cells which were culture in parallel with NR15 cells without EBV-reactivation. We concluded that it is the highly recurrent reactivations of EBV, but neither just a primary reactivation nor EBV-latent infection, may intimately involve in carcinogenesis of nasopharyngeal epithelial cells with the progressive genome instabilities and the accumulation of genetic mutations. Experiment Overall Design: Samples of four sources were analyzed. The NP1 cells denoted the EBV-latently infected nasopharyngeal carcinoma cell lines, NA cells, with low-passage-number and mock-treated. The NR1 denoted the NA cells harboring one time of EBV reactivation. The NR15 cells denoted the NA cells harboring fifteen times of EBV reactivation. The NP15 cells denoted the NA cells cultured in parallel with NR15 (experienced 15 times of passages) without EBV-reactivation. Genomic DNAs extracted from NP15, NR1 and NR15 cells were used as experimental samples and subjected to Cy5-labeling reactions. Genomic DNAs extracted from NP1 cells were used as the common reference samples subjected to Cy3-labeling reactions. All three experiments were verified by dye-swap design where the targets labeling conditions were exchanged, NP1 labeled with Cy5, and NP15, NR1 or NR15 labeled with Cy3.

Dataset Information

Gene expression profiling of age-related EBV-positive B-cell lymphoproliferative disorders uncovers alterations in characteristic oncogenetic pathways: possible implications for pathogenesis

Publications

Gene expression profiling of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways.

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