title: Normal thyrocytes vs papillary vs anaplastic thyroid carcinomas

city: Brussels

first: Gil

last: Tomas

address: 808 route de Lennik

department: IRIBHM

country: Belgium

institute: ULB

summary: We profiled the gene expression of 11 anaplastic thyroid carcinomas (ATC), 49 papillary thyroid carcinomas (PTC) and 45 normal thyroids (N)

overall_design: We hibridized a series of anaplastic thyroid carcinomas (ATC) and papillary thyroid carcinomas (PTC) onto Affymetrix U133 Plus 2.0 arrays. ATCs were obtained from different hospitals in France and Belgium. Paired RNA samples of PTCs and non-tumoral thyroid tissues were obtained from Ukraine via the Chernobyl Tissue Bank (www.chernobyltissuebank.com). Diagnoses were confirmed by the members of the International Pathology Panel of the Chernobyl Tissue Bank.

first: Detours

last: Vincent


title: Expression data comparing PLZF+/+, PLZF +/lu, PLZF lu/lu gammadelta NKT cells

status: Public on Nov 09 2012

city: Boston

first: Michael

last: Gleimer

state: MA

address: SM736, 450 Brookline Ave

department: CIA

country: USA

institute: DFCI

summary:
Natural killer (NKT) T cells exhibit tissue distribution, surface phenotype, and functional responses that are strikingly different from those of conventional T cells. The transcription factor PLZF is responsible for most of these properties, as its ectopic expression in conventional T cells is sufficient to confer to them an NKT-like phenotype. The molecular program downstream of PLZF, however, is largely unexplored.
Here we report that PLZF regulates the expression of a surprisingly small set of genes, many with known immune functions. This includes several established components of the NKT cell developmental program.

overall_design: Transcriptional program downstream of PLZF in gammadelta NKT cells was analyzed by comparing wt, heterozygous and PLZF-deficient gammadelta NKT cells

first: M

first: H

last: von Boehmer

first: T

last: Kreslavsky


title: DNA methylation changes are a late event in Acute Promyelocytic Leukemia and coincide with loss of transcription factor binding (Illumina Methylation)

status: Public on Nov 08 2012

city: Heidelberg

first: Christian

last: Rohde

address: Im Neuenheimer Feld 410

country: Germany

institute: Heidelberg University

type: Methylation profiling by genome tiling array

summary: The origin of aberrant DNA methylation in cancer remains largely unknown. In this study, we elucidated the DNA methylome in primary Acute Promyelocytic Leukemia (APL) and the role of PML-RARa in establishing these patterns. APL patients showed increased genome-wide DNA methylation with higher variability than healthy CD34+ cells, promyelocytes and remission bone marrow. A core set of differentially methylated regions in APL was identified.  Age at diagnosis, Sanz score and Flt3-mutation status characterized methylation subtypes. Transcription factor binding sites, e.g. c-myc binding sites were associated with low methylation. SUZ12 and REST binding sites identified in embryonic stem cells were, however, preferentially DNA hypermethylated in APL. Unexpectedly, PML-RARa binding sites were also protected from aberrant DNA methylation in APL.  In line, myeloid cells from pre-leukemic PML-RARa knock-in mice did not show altered DNA methylation and expression of PML-RARa in hematopoietic progenitor cells prevented differentiation without affecting DNA methylation. ATRA treatment of APL blasts did also not result in DNA methylation changes. These results suggest that aberrant DNA methylation is associated with leukemia phenotype but not required for PML-RARa-mediated initiation of leukemogenesis.

overall_design: Bisulphite converted DNA from the 10 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

first: Till

last: Schoofs

first: Carsten

last: Müller-Tidow


title: Expression data from Leishmania major infected human dendritic cells

city: Notre Dame

first: Michelle

middle: A

last: Favila

state: IN

address: 210 Galvin Life Science Center

department: Biology

institute: University of Notre Dame

summary:
Leishmania major infected human dendritic cells (DCs) exhibit a marked induction of IL-12 ultimately promoting a robust Th1-mediated response associated with parasite killing and protective immunity.  In this study, we utilized Affymetrix Genechips to globally assess the host cell genes and pathways associated with L. major infection during early infection (2, 4, 8, and 24 hrs) in human myeloid-derived DCs.  Bioinformatic analyses of the hybridized microarray chips identified 728 genes, represented by 848 unique probe sets, which, when compared to uninfected samples were observed to be significantly differentially expressed by one-way ANOVA.  Altogether, the data provide a genome-wide perspective on the transcriptional influences Leishmania species exert within human DCs during early infection, and provides a platform for further investigations toward functionally characterizing candidate genes of importance to the IL-12 based immune response to infections.
In the current study, we further investigate the L. major infected DC transcriptional during early time points after infection via microarray analysis.

overall_design: The cRNAs for each L. major infected time point (2, 4, 8, 24 hrs) including an uninfected sample (2 hrs), from three individual donors, were extracted and hybridized to 15 individual human HG-U133 Plus2.0 Affymetrix microarray gene chips, whereby each chip represented the expression profile for one donor at a given infection time point.

first: Mary

last: McDowell


title: Expression data from CD11c+ mDCs in HIV infection

status: Public on Nov 07 2012

city: Davis

first: Lauren

last: Nagy

state: CA

address: 451 Health Sciences

department: Medical Microbiology and Immunology

institute: University of California-Davis

summary:
CD11c+ Myeloid Dendritic Cells (mDCs) were isolated from the peripheral blood mononuclear cells (PBMCs) of HIV uninfected and HIV infected subjects.
The expression of CD11c+ mDCs was accessed to determine how HIV infection may play a role on the expression profiles of these cells. mDCs are known to play a role in antigen presentation, and thus are pivotal in immune sensing and priming of the adaptive immune response. We wanted to see if the change in immune system function during chronic HIV infection may be due to defects in this cell subtype.
We used microarray analysis to detail the global program of gene expression underlying changes in mDC function during HIV infection.

overall_design: PBMCs were isolated from HIV uninfected and HIV infected blood samples. CD11c+ cells were sorted from the whole PBMC population by magnetic bead sorting (anti-CD11c antibody bound to a magnetic bead inclubated with whole PBMCs). RNA was isolated from this sorted population to get the gene expression of this subtype of cells.

first: Satya

last: Dandekar


title: Expression profiles in testis of mouse inter-subspecific hybrids

city: Prague

first: Petr

last: Simecek

state: Not Applicable

address: Vídeňská 1083

department: Department of Mouse Molecular Genetics

country: Czech Republic

institute: Institute of Molecular Genetics of the ASCR, v. v. i.

summary: According to Dobzhansky-Muller model, hybrid sterility is a consequence of independent evolution of related taxa resulting in incompatible interaction during gametogenesis of their hybrids. We proposed that asynapsis of heterospecific chromosomes in meiotic prophase provides a general and recurrently evolving trigger for the meiotic arrest of  interspecific F1 hybrids. We used genome-wide expression profiling to quantify misexpression of Chr X and Chr Y genes.

overall_design: The total RNA (20–30 ng) samples were extracted from 14.5 days juvenile testes (pool of 4 samples), converted to cDNA using the Affymetrix 3 IVT Express Kit and hybridized to Affymetrix Mouse Gene 1.0ST GeneChips (core facility of the Institute of Molecular Genetics AS CR, Prague, Czech Rep.)  We visually checked intensity histograms, boxplots and PCA graph and excluded one PWDxPWK sample that was a clear outlyer on all QC graphs (not shown).

first: Tanmoy

last: Bhattacharyya

first: Jiri

last: Forejt


title: YWHAZ is an Invasion and Metastasis promoting genes of Lung cancer

city: Taipei

first: Sung-Liang

last: Yu

address: Jen Ai Road Section1

department: Clinical Laboratory Sciences and Medical Biotechnology

country: Taiwan

institute: National Taiwan University

summary: Metastasis is a major cause leading to mortality for lung cancer patients. We identified YWHAZ as a potential metastasis-promoting candidate and found that overexpression of YWHAZ promotes lung cancer cell proliferation, anchorage-independent growth, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. It not only increases cell protrusions and branchings but also induces epithelial-mesenchymal transition. Most importantly, YWHAZ protein could prevent £]-catenin from ubiquitination via its association with £]-catenin and enhance slug transcriptional activity which is regulated by £]-catenin/TCF signaling pathway. Moreover, YWHAZ expression was higher in tumors than in adjacent normal tissues in 63 Non-small-cell lung cancer (NSCLC) patients. NSCLC patients with high YWHAZ expressing tumors had shorter overall survival than those with low-expressing tumors. We conclude that YWHAZ play a critical role in promoting NSCLC metastasis.

overall_design: In this investigation, we used a lung cancer invasion cell model to identify the genes involved in cancer progression. YWHAZ is a potential oncogene whose expression is correlated to the survival of patients with breast, prostate and liver cancers. However, the role of YWHAZ in lung caner progression has not been reported, particularly in metastasis. Here, YWHAZ was ectopically expressed in lower invasive lung cancer cell line its impact on colonogenesis, migration and invasiveness was assessed. The underlying mechanism was explored by YWHAZ-expressed transfectants and microarrays and the clinical relevance was evaluated by quantitative RT-PCR.


title: Functional MYCN signature predicts outcome of neuroblastoma irrespective of MYCN amplification.

status: Public on Nov 05 2012

city: Amsterdam

first: Richard

last: Volckmann

state: Noord-Holland

address: van der Boechorststraat 6a

department: Laboratory of Experimental Oncology and Radiobiology

country: Netherlands

institute: msterdam UMC and University of Amsterdam

summary: Neuroblastoma is a pediatric tumor of the sympathetic nervous system. MYCN (V-myc myelocytomatosis viral-related oncogene, neuroblastoma derived [avian]) is amplified in 20% of neuroblastomas, and these tumors carry a poor prognosis. However, tumors without MYCN amplification also may have a poor outcome. Here, we identified downstream targets of MYCN by shRNA-mediated silencing MYCN in neuroblastoma cells. From these targets, 157 genes showed an expression profile correlating with MYCN mRNA levels in NB88, a series of 88 neuroblastoma tumors, and therefore represent in vivo relevant MYCN pathway genes. This 157-gene signature identified very poor prognosis tumors in NB88 and independent neuroblastoma cohorts and was more powerful than MYCN amplification or MYCN expression alone. Remarkably, this signature also identified poor outcome of a group of tumors without MYCN amplification. Most of these tumors have low MYCN mRNA levels but high nuclear MYCN protein levels, suggesting stabilization of MYCN at the protein level. One tumor has an MYC amplification and high MYC expression. Chip-on-chip analyses showed that most genes in this signature are directly regulated by MYCN. MYCN induces genes functioning in cell cycle and DNA repair while repressing neuronal differentiation genes. The functional MYCN-157 signature recognizes classical neuroblastoma with MYCN amplification, as well as a newly identified group marked by MYCN protein stabilization.

overall_design: IMR32 was transduced with control or shMYCN virus (duplo). For each experiment 3 time points were analyzed and 2 no virus controls.

first: Linda

middle: J

last: Valentijn

first: Franciska

last: Haneveld


title: Gene expression data from mouse liver

status: Public on Nov 06 2012

city: Nashville

first: Viswanathan

last: Saraswathi

state: TN

address: 702 Light Hall, 23rd Ave and Pierce

institute: Vanderbilt University

summary: We used microarray analysis to examine which genes are differentially expressed in mice that received a combination of fish oil and indomethacin.

sample_organism:
Mus musculus
Mus sp.

overall_design: We fed low density lipoprotein receptor knock-out (LDLR-/-) mice with 6% of olive oil (control) or fish oil diets in the presence or absence of indomethacin for 12 weeks. We collected total RNA from liver samples and pooled 6 RNA samples in each group for Affymetrix microarrays.

first: Saraswathi

last: Viswanathan


title: Gene knockdown and overexpression of 402C>G FOXL2 in COV434 and KGN cells

city: Auckland

first: Roseanne

last: Rosario

address: 85 Park Road, Grafton

country: New Zealand

institute: University of Auckland

summary: Despite their distinct biology, granulosa cell tumours (GCTs) are treated the same as other ovarian tumours.  Intriguingly, a recurring somatic mutation in the transcription factor Forkhead Box L2 (FOXL2) 402C>G has been found in nearly all GCTs examined.  This investigation aims to identify the pathogenicity of mutant FOXL2 by studying its altered transcriptional targets. The expression of mutant FOXL2 was reduced in the GCT cell line KGN, and wildtype and mutant FOXL2 were overexpressed in the GCT cell line COV434. Comparisons were made between the transcriptomes of control cells and cells altered by FOXL2 knockdown and overexpression, to detect potential transcriptional targets of mutant FOXL2.      Comparisons were made between the transcriptomes of control cells and cells altered by FOXL2 knockdown and overexpression, to detect potential transcriptional targets of mutant FOXL2.

overall_design: Mutant FOXL2 was silenced in KGN cells with the use of siRNA and a non-targetting siRNA control. Wildtype and mutant FOXL2 were overexpressed in COV434 cells with the use of overexpression plasmids and an empty plasmid control.  Each experiment was performed in triplicate.  Total RNA was harvested at 24h post transfection and hybridised to Affymetrix U133 plus 2.0 arrays.

first: Hiromitsu

last: Araki

first: Cristin

middle: G

last: Print

first: Andrew

middle: N

last: Shelling


title: Genome-wide DNA methylation profiling predicts relapse in childhood B-cell acute lymphoblastic leukemia

city: L'Hospitalet de Llobregat

first: Manel

last: Esteller

state: Barcelona

address: Hospital Duran i Reynals Av. Gran Via s/n km, 2.7

department: PEBC

country: Spain

institute: IDIBELL

summary: Although the 5-year survival of childhood Acute Lymphoblastic Leukemia (ALL) exceeds 80%, a group of patients presents poor prognosis due to early relapse. To date, treatment strategies are defined by cytogenetically-based subtype categorization. However, ALL patients without chromosomal translocations associated with poor prognosis lack diagnostic markers to adjust specific therapies. DNA methylation alteration is a frequent event in cancer with high potential in diagnosis, prognosis and prediction of drug response. Hence, we aimed to characterize childhood B-ALLs without Philadelphia (BCR-ABL) and MLL translocations based on their DNA methylation profile of more than 450,000 CpG sites to improve accuracy in prognosis and treatment strategies.

overall_design: DNA was quantified by Quant-iT PicoGreen dsDNA Reagent (Invitrogen) and the integrity was analyzed in a 1.3% agarose gel. Bisulfite conversion of 600 ng of each sample was performed according to the manufacturer's recommendation for the Illumina Infinium Assay. Effective bisulfite conversion was checked for three controls that were converted simultaneously with the samples. 4 ul of bisulfite-converted DNA were used to hybridize on Infinium HumanMethylation 450 BeadChip, following the Illumina Infinium HD Methylation protocol. Chip analysis was performed using the Illumina HiScan SQ fluorescent scanner. The intensities of the images were extracted using GenomeStudio (2010.3) Methylation module (1.8.5) software. The methylation score of each CpG is represented as a beta value.

first: Juan

last: Sandoval


title: Expression data from HeLa cells treated with Casiopeina Cas-II-gly

status: Public on Oct 31 2012

city: Mexico City

first: Karol

last: Baca Lopez

address: Periferico sur

country: Mexico

institute: National Institute of Genomic Medicine

summary:
Copper-based chemotherapeutic compounds Casiopeinas, have been presented as able to promote selective programmed cell death in cancer cells, thus being proper candidates for targeted cancer therapy. DNA fragmentation and apoptosis -in a process mediated by reactive oxygen species- for a number of tumor cells, have been argued to be the main mechanisms. However, a detailed functional mechanism (a model) is still to be defined and interrogated for a wide variety of cellular conditions; before establishing settings and parameters needed for their wide clinical application.
Microarrays were used to determine the expression profile from HeLa cells in order to propose a model for the role played by intrinsic apoptosis triggered by the oxidative stress caused by Cas-II-gly.

overall_design: The cervix-uterine cell line HeLa  was maintained at 37C in 5% CO2  under sterile conditions in Dulbecco's modified Eagle medium (DMEM, Sigma), supplemented with 10% fetal bovine serum (Sigma). Cells were treated with Cas II-gly in 96-well microplates by 6 h.  HeLa cells whole genome gene expression experiments (triplicates for cases/controls) were performed in total mRNA extracted under the GPL570 protocol.

first: Alejandra

middle: I

last: Valencia-Cruz

first: Laura

last: Uribe-Figueroa

first: Rodrigo

last: Galindo-Murillo

last: Baca-Lopez

first: Anllely

last: Gutierrez

first: Adriana

last: Vazquez-Aguirre

first: Lena

last: Ruiz-Azuara

first: Enrique

last: Hernandez-Lemus

first: Carmen

last: Mejia


title: Thalidomide in Total Therapy 2 Overcomes Inferior Prognosis of Myeloma with Low Expression of the Glucocorticoid Receptor Gene NR3C1

city: Little Rock

first: Christoph

last: Heuck

state: AR

address: 4301 W Markham

department: Myeloma Institute for Research and Therapy

institute: University of Arkansas for Medical Sciences

summary: Purpose: Because dexamethasone remains a key component of myeloma therapy, we wished to examine the correlation of baseline and relapse expression levels of the glucocorticoid receptor gene NR3C1 with other clinical features.  Experimental Design:  We investigated the clinical impact of gene expression profiling (GEP)–derived expression levels of NR3C1 in 351 patients with GEP data available at baseline and in 130 with data available at relapse, among 668 subjects accrued to Total Therapy 2 (TT2).

overall_design: The effect of the expression of NR3C1 at baseline (previously published under GSE2685) and at relapse was analyzed  in the context of treatment (thalidomide vs. no thalidomide) and other clinical parameters.


title: Expression data from primary central nervous system lymphoma (PCNSL) patients

city: Kyoto

first: Ryuya

last: Yamanaka

address: 465 Kajii-cho, Kamigyoku

country: Japan

institute: Kyoto Prefectural University of Medicine

summary: This study aimed to define the genes associated with PCNSL patient survival. Expression profiling was performed on 34 PCNSLs. A gene classifier was developed.

overall_design: Thirty-four PCNSL patients were selected for RNA extraction and hybridization on Affymetrix microarrays.

first: Atsushi

last: Kawaguchi


title: FoxO6 regulates memory consolidation and synaptic function.

city: Stanford

first: Anne

last: Brunet

state: California

address: 300 Pasteur Drive,

department: Genetics

institute: Stanford University

summary: We used microarrays to assess gene expression differences in the hippocampus between FoxO6 mutant and wild-type siblings before (basal) or after novel object learning.

overall_design: The cohort of basal mice were housed individually for at least 3 days prior to tissue harvesting. The mice used to collect hippocampal samples after the object learning task were handled daily in the procedure room, prior to the object learning task. 24 hours before the object learning task, each mouse was individually habituated to the empty novel object arena for 10 min. On the days of the novel object learning task and the empty arena habituation, the mice were transferred to the procedure room and acclimatized for 60 min. For the novel object learning task, the mice were allowed to explore two identical and novel objects for 10 min in a 70 x 70 x 70 cm black plastic arena with a white PVC vinyl material on the base. After the object exploration, mice were transferred to an empty cage, and were euthanized after 60 min. The brains were dissected and incubated in ice-cold RNAlater (Ambion) for 24 hours at 4ºC. The brains were then rapidly frozen in O.C.T. Tissue-Tek (Sakura) at -80ºC. Coronal brain sections (300 µm) were made using a microtome (Microm), the hippocampus was finely dissected and collected into ‘RNA lysis buffer’ (Ambion), and homogenized for 30 sec using a rotar-stat homogenizer. Total RNA was extracted using the RNAqueous column (Ambion) following the manufacturer’s protocol.

first: Dervis

last: Salih


title: Identification and Characterization of Subpopulations within Human Embryonic Stem Cell Lines

status: Public on Nov 01 2012

city: RTP

first: NIEHS

last: Microarray Core

state: NC

address: 111 T.W. Alexander Drive

department: DIR

institute: NIEHS

summary: The Microarray study was designed to characterize the whole genome transcription profile of two subpopulations of H1 human embryonic stem cells we identified by size using flow cytometry.The heterogeneous nature of stem cells is an important issue in both research and therapeutic use in terms of directing cell lineage differentiation pathways, as well as self-renewal properties. Using flow cytometry we have identified two distinct subpopulations by size within the H1 and BGN1 human embryonic stem (hES) cell lines. Both populations express stem the cell markers Oct-4, Nanog, Tra-1-60, Tra-1-80 and SSea-4 and express very low levels of differentiation markers common to the three germ layers. To investigate if the two populations possessed different transcription profiles, we performed whole genome microarray analysis, and identified approximately 400 genes with significant differential expression (p<0.01). Cloning experiments indicate that both populations are able to repopulate each other and maintain the parental population. The large cell population responds to retinoic acid (RA) differentiation as evidenced by greater than a 50% loss of gated cell number and loss of Oct-4 expression; while the small cell population number does not change and maintains Oct-4 protein expression.  The presence of these two populations could be vitally important with respect to stem cell therapy and research as they respond differently to differentiation signals, which may be important in directing stem cell differentiation for disease therapy.

overall_design: Four independent biological sort repeats for each subpopulation of large and small were hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays (Affymetrix, Santa Clara, CA). Starting with 1ug of total RNA, biotin-labeled cRNA was produced using the Affymetrix 3’ Amplification One-Cycle Target labeling kit according to manufacturer’s protocol. For each array, 15ug of amplified cRNAs were fragmented and hybridized to the array for 16 hours in a rotating hybridization oven using the Affymetrix Eukaryotic Target Hybridization Controls and protocol. Slides were stained and washed as indicated in the Antibody Amplification Stain for Eukaryotic Targets protocol using the Affymetrix Fluidics Station FS450. Arrays were then scanned with an Affymetrix Scanner 3000. Data was obtained using the Genechip® Operating Software and imported into the Rosetta Resolver system (version 7.1)(Rosetta Inpharmatics LLC, Seattle, WA).  Biological replicates were combined using an error-weighted average as described in Weng et al. 23 P-values and fold changes based on the ratio of small large were generated in Resolver and used as a threshold for selecting differentially expressed genes

first: L

last: Annab

first: C

middle: D

last: Bortner

first: J

middle: B

last: Collins

first: R

middle: R

last: Shah

first: D

last: Dixon

first: T

middle: K

last: Archer


title: The NIH Human Pluripotent Stem Cell Database (Affymetrix, mRNA)

city: Bethesda

first: Kory

last: Johnson

state: MD

address: 10/3B01, 9000 Rockville Pike

department: DIR IT & Bioinformatics

institute: NINDS/NIH

summary: To broaden the appeal of the NIH Stem Cell Database, we analyzed a subset of undifferentiated human embryonic stem cell lines (5 lines in duplicate) on the Affymetrix platform. One standard culture protocol was used in conjunction with rigorous quality control. Expanded description of methods used and are available at: http://stemcelldb.nih.gov.

overall_design: 12 samples: 10 human ESC (UNDIFFiferentiated) and 2 processing controls (UniRef).

first: Barbara

middle: S

last: Mallon

first: Josh

last: Chenoweth

first: Rebecca

last: Hamilton

first: Paul

last: Tesar

first: Amarendra

last: Yavatkar

first: Leonard

last: Tyson

first: Yang

middle: C

last: Fann

first: Kye

middle: Y

last: Park

first: Kevin

last: Chen

first: Ronald

last: McKay


title: In vivo NCL-targeting affects breast cancer aggressiveness through miRNA regulation [Affymetrix]

status: Public on Nov 02 2012

city: Bellinzona

first: Luciano

last: Cascione

state: Ticino

address: Via Chiesa 5

department: Lymphoma & Genomics Research Program

country: Switzerland

institute: IOR

summary: Numerous studies have described the altered expression and the causal role of miRNAs in human cancer. However, to date efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here, we find that Nucleolin (NCL), a major nucleolar protein, post-transcriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, causally involved in breast cancer initiation, progression and drug-resistance. We also show that NCL is commonly overexpressed in human breast tumors, and its expression correlates with that of NCL-dependent miRNAs. Finally, this study indicates that NCL-binding guanosine-rich aptamers affect the levels of NCL-dependent miRNAs and their target genes, reducing breast cancer cell aggressiveness, both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer.

overall_design: MCF7 cells were treated with the control drug or AS1411 aptamer. After 72hours total RNA was collected and analyzed by Affymetrix U133 plus.

first: Flavia

last: Pichiorri

first: Dario

last: Palmieri

first: Luciana

last: De Luca

first: Jessica

last: Consiglio

first: Jia

last: You

first: Alberto

last: Rocci

first: Tiffany

last: Talabere

first: Claudia

last: Pivan

first: Alessandro

last: Lagana

first: Jingwen

last: Guan

first: Pierluigi

last: Gasparini

first: Veronica

last: Balatti

first: Vincenzo

last: Coppola

first: Craig

last: Hofmeister

first: Guido

last: Marcucci

first: John

last: Byrd

first: Stefano

last: Volinia

first: Charles

middle: L

last: Shapiro

first: Michael

last: Freitas

first: Carlo

middle: M

last: Croce


title: T-bet regulated genes in KG1 cells

status: Public on Oct 30 2012

city: Frankfurt

first: Malte

last: Bachmann

address: Theodor Stern Kai 7

department: General Pharmacology

institute: University Hospital Frankfurt

summary:
T-bet is pivotal for initiation and perpetuation of Th1 immunity. Identification of novel T-bet regulated genes is crucial for further understanding the biology of this transcription factor.
By combining siRNA technology with genome-wide mRNA analysis, we sought to identify new T-bet regulated genes in IL-18-activated KG1 cells.

overall_design: KG1 cells were transfected with either control-siRNA (siRNAc) or siRNA targeting T-bet (siRNA-Tbet) and thereafter stimulated with IL-18. Total RNA  was evaluated by genome-wide analysis using the Affymetrix GeneChip® Array System.

first: Heiko

last: Muehl


title: The NIH Human Pluripotent Stem Cell Database

first: Kory

last: Johnson

type:
Expression profiling by array
Non-coding RNA profiling by array
Methylation profiling by array
Genome variation profiling by SNP array
SNP genotyping by SNP array

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Correlated alterations in genome organization, histone methylation, and DNA-lamina interactions in Hutchinson-Gilford progeria syndrome (expression)

city: Worcester

first: Rachel

middle: Patton

last: McCord

address: 364 Plantation St. LRB 570M

department: Program in Gene Function and Expression

institute: University of Massachusetts Medical School

summary: Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease that is frequently caused by a de novo point mutation at position 1824 in LMNA. This mutation activates a cryptic splice donor site in exon 11, and leads to an in-frame deletion within the prelamin A mRNA and the production of a dominant negative lamin A protein, known as progerin. Here we show that HGPS cells experience genome-wide alterations in patterns of H3K27me3 deposition, changes in the associations of genomic loci with nuclear lamin A/C, and, at late passages, genome-wide loss of spatial compartmentalization of active and inactive chromatin domains that characterizes chromosome folding in normal cells. We further demonstrate that the H3K27me3 changes associate with gene expression alterations in HGPS cells. Our results support a model that the accumulation of progerin in the nuclear lamina leads to altered H3K27me3 marks in heterochromatin, possibly through the down-regulation of EZH2, and disrupts heterochromatin-lamina interactions. These changes may then lead to the genomic disorganization and changes in transcriptional regulation we observe in HGPS fibroblasts.

overall_design: We analyzed gene expression of primary fibroblasts of a Hutchinson-Gilford progeria syndrome patient, a healthy age-matched control, and the patient's healthy father using the Affymetrix GeneChip Human Genome U133 Plus 2.0 Array platform. Arrays were filtered and normalized using RMA. Two replicates were performed.

middle: P

first: Ashley

last: Nazario-Toole

first: Haoyue

last: Zhang

first: Peter

last: Chines

first: Ye

last: Zhan

last: Erdos

first: Francis

last: Collins

first: Job

last: Dekker

first: Kan

last: Cao


title: Fate determination of adult human glial progenitor cells

city: Buffalo

first: Fraser

middle: James

last: Sim

state: NY

address: 3435 Main Street

department: Pharmacology

institute: University at Buffalo

summary: Glial progenitor cells comprise the most abundant population of progenitor cells in the adult human brain. They are responsible for CNS remyelination, and likely contribute to the astrogliotic response to brain injury and degeneration as well. Adult human GPCs are biased to differentiate as oligodendrocytes and elaborate new myelin, and yet they retain multilineage plasticity, and can give rise to neurons as well as astrocytes and oligodendrocytes once removed from the adult parenchymal environment. GPCs retain strong mechanisms for cell-autonomous self-renewal, and yet both their phenotype and fate may be dictated by their microenvironment. Using the transcriptional profiles of acutely isolated GPCs, we have begun to understand the operative ligand-receptor interactions involved in these processes, and have identified several key signaling pathways by which adult human GPCs may be reliably instructed to either oligodendrocytic or astrocytic fate. In addition, we have noted significant differences between the expressed genes and dominant signaling pathways of fetal and adult human GPCs, as well as between rodent and human GPCs. The latter data in particular call into question therapeutic strategies predicated solely upon data obtained using rodents, while perhaps highlighting the extent to which evolution has been attended by the phylogenetic modification of glial phenotype and function.

overall_design: Human adult brain dissociates were sorted for one of three markers, either GLT1 (astrocyte, n =3), CD11b (microglia, n=4) or A2B5 (glial progenitor cell, n=7). In addition to positively selected, the negative fraction and unsorted dissociates were collected as matched controls for each sort.

first: Ditte

last: Lovatt

first: Miaken

last: Nedergaard

first: Steven

last: Goldman


title: FGFR3-shRNA induced transcriptional changes in RT112 bladder cancer cells

city: South San Francisco

first: Jinfeng

last: Liu

address: 1 DNA Way, MS93

department: Bioinformatics and Computational Biology

institute: Genentech Inc.

summary: Aberrant activation of FGFR3 via overexpression or mutation is a frequent feature of bladder cancer; however, its molecular and cellular consequences and functional relevance to carcinogenesis are not well understood.  In this study with a bladder carcinoma cell line expressing inducible FGFR3 shRNAs, we sought to identiy transcriptional targets of FGFR3 and investigate their contribution to bladder cancer development.

overall_design: Bladder cancer cell line RT112 was transduced with a doxycycline-inducible control EGFP shRNA or three independent FGFR3 shRNAs, designated FGFR3 shRNA 2-4, FGFR3 shRNA 4-1 and FGFR3 shRNA 6-16.  These four cell lines were treated with or without doxycycline for 48 hr to deplete FGFR3 protein prior to the isolation of mRNA for microarray analysis.  Genes that were differentially expressed after doxycycline induction in all three FGFR3-depleted cell lines but not in the control cell line were considered potential FGFR3-regulated genes.  Each treatment group was run in triplcates, and there are 24 samples.

first: Zora

last: Modrusan

first: Xiangnan

last: Du

first: Jing

last: Qing


title: Differential Gene Expression in Granulosa Cells from Polycystic Ovary Syndrome Patients with and without Insulin Resistance:  Identification of Susceptibility Gene Sets through Network Analysis

city: Delhi

first: Rita

last: Singh

address: Department of Zoology

department: Department of Zoology

country: India

institute: University of Delhi

summary: Polycystic ovary Syndrome (PCOS) is a heterogeneous endocrine disorder that shows evidence of genetic predidposition among affected individuals. We have utilized the Microarray data from  granulosa cells of normal and PCOS women for network construction.

overall_design: Human granulosa cells were isolated from ovarian aspirates from normal and PCOS women undergoing IVF and for each sample, RNA was extracted and hybridized to an Affymetrix GeneChip.

first: Surleen

last: Kaur

first: Kellie

last: Archer

first: M

last: Devi

first: Alka

last: Kriplani

first: Jerome

middle: F

last: Strauss


title: Expression data from quiescent cells and cycling cells isolated from Multicellular aggregates of lymphoma cells (MALC)

status: Public on Oct 27 2012

city: TOULOUSE

first: Pauline

last: GRAVELLE

address: CHU Purpan, Pavillon Lefebvre

country: France

institute: INSERM UMR1037

summary: Follicular Lymphomas are blood tumors growing as spheres in patients. Before this study, there was no experimental model mimicking the 3D organization of these in vivo tumors. We develop such a model, called MALC, and observed a progressive enrichment in quiescent cells in these with time of culture; these cells were sorted, as their cycling counterparts, and their transcriptomes were compared. We used microarrays to detail the differential global gene expression profile between quiescent and cycling cells isolated from MALC.

overall_design: 14 days-old MALC were stained with pyronin Y and quiescent and cycling subpopulations sorted were selected for RNA extraction and hybridization on Affymetrix U133+ 2.0 microarrays.

last: Gravelle


title: Down-regulation of Interferon signature in systemic lupus erythematosus patients by active immunization with Interferon alpha-Kinoid

city: Brussels

first: Bernard

middle: Robert

last: Lauwerys

address: Avenue Hippocrate 10

department: Institut de Recherches Expérimentales et Cliniques

institute: Université catholique de Louvain

summary:
We performed a phase I/II, randomized, double-blind, placebo-controlled dose-escalation study to examine the safety, immunogenicity, and biological effects of active immunization with interferon alpha-Kinoid (IFN-K) in systemic lupus erythematosus (SLE) patients. Women 18-50 years of age with mild to moderate SLE were immunized with three (n=10) or four doses (n=9) of 30, 60, 120, 240 microgram IFN-K or saline.
Anti-IFNalpha antibodies were detected in all IFN-K-immunized patients. Transcriptomic analysis separated patients at baseline into type I IFN signature-positive and -negative groups. IFN-K induced higher anti-IFNalpha titers in signature-positive than in signature-negative patients and, in signature-positive patients, reduced the expression of IFN-induced genes. The decrease in IFN score correlated with the anti-IFNalpha antibody titers, and with baseline IFN score.

overall_design: IFN-K or placebo was administered at day 0, day 7, day 28 in all patients. Half the subjects received a fourth injection at day 84 (see treatment protocol)

first: Pierre

last: Vandepapelière

first: Frédéric

middle: A

last: Houssiau


title: Cell growth in aggregates determines gene expression, proliferation, survival and chemoresistance of Follicular Lymphoma


title: Expression Data from hypothalamus of IL-6 deficient mice and their wild-type littermates following intraperitoneal LPS challenge

status: Public on Oct 29 2012

city: Linköping

first: Namik

last: Hamzic

address: Linköpings Universitet

department: Institution for clinical and experimental medicin

country: Sweden

institute: University of Health

summary: IL-6 has been described to be a critical cytokine in mediating the febrile response because neither IL-6 knockout mice injected with peripheral lipopolysaccharide (LPS) or IL-1β, nor animals treated with IL-6 antiserum develop fever. However, the fever response is developed in IL-6 KO mice following intracerebroventricular administration of Prostaglandin E2 which is the principal mediator of the febrile response.

overall_design: We performed a genome-wide microarray expression comparison between LPS-treated WT and IL-6 KO mice to evaluate if there were any differentially expressed genes in mice devoid of IL-6 that can explain the absence of fever response.


title: Expression data from follicular lymphoma cells cultured either in suspension either as Multicellular aggregates of lymphoma cells (MALC)

summary: Follicular Lymphomas are blood tumors growing as spheres in patients. Before this study, there was no experimental model mimicking the 3D organization of these in vivo tumors. We develop such a model, called MALC, and performed a pan-genomic comparative analysis between MALC and classical suspension cultures. We used microarrays to detail the global gene expression profile induced by aggregated growth of lymphoma cells.

overall_design: 10 days-old MALC and suspension RL cells were selected for RNA extraction and hybridization on Affymetrix U133+ 2.0 microarrays.

first: Christine

last: Jean


title: Expression analysis of the glucose deprivation-induced human tumor cell responses

status: Public on Oct 25 2012

city: Ann Arbor

first: yugang

last: wang

state: MI

address: 1011 N Universtiy Dr., room 5205

department: BMS

institute: University of Michigan

summary: The tumor microenvironment is characterized by low glucose and hypoxia. It is well known that changes in the tumor microenvironment, such as hypoxia and low glucose, can increase the production of VEGF. Although the role of hypoxia in the regulation of VEGF production is well understood, the mechanism linking glucose deprivation (GD) to tumor growth and angiogenesis is unclear. Here, GD (a physiological stimulus) was used to treat human tumor cells. The transcriptional reprogramming of tumor cells by GD was measured with microarray technology to provide a comprehensive analysis of the gene expression profile underlying the GD treatment. Our study suggested that GD initiates an angiogenic switch by increasing the expression of proangiogenic mediators  (VEGF, FGF2, IL6, etc.) and decreasing the expression of angiogenesis inhibitors (THBS1, CXCL14 and CXCL10). The markers of Unfolded Protein Response (UPR) (Grp78/Bip, CHOP, ATF4, etc.) were significantly increased. The above results suggest GD may regulate angiogenesis through activation of the UPR.

overall_design: UM-SCC-81B cells (human oral squamous cell carcinoma cell line) were treated with glucose deprivation (GD) for 4 hours (UM-SCC-81B-GD-4) and 24 hours (UM-SCC-81B-GD24). Cells without treatment were used as a non-treatment control (UM-SCC-81B-NT). Each sample was analyzed once, i.e., without biological replicates. The expression of the genes of interest was confirmed with real-time PCR, ELISA and Western blot.

first: Yugang

last: Wang

first: Yu

last: Ning

first: Taocong

last: Jin

first: Goleeta

last: Alam

first: Peter

middle: J

last: Polverini


title: Transcriptome profiling for changes upon Lin28a knockdown in mouse embryonic stem cell (A3-1) [Affymetrix]

city: Seoul

first: Hyeshik

last: Chang

state: South Korea

address: Building 203 Room 525, School of Biological Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu

department: School of Biological Sciences

country: South Korea

institute: Seoul National University

summary: LIN28A is a highly-conserved RNA-binding protein which is known to be involved in embryonic development, stem cell maintenance and proliferation. LIN28A is expressed in various types of cancer, and they are associated with advanced tumor malignancy. In embryonic stem cell, LIN28A specifically binds to let-7 precursors to suppress biogenesis of the let-7 microRNA family. In addition, LIN28A was reported to bind several mRNAs such as Oct4, cyclin A/B and histone H2A to activate their translation. For comprehensive understanding of the interaction between LIN28A and their target RNAs, we exploited UV-crosslinking and immunoprecipitation (CLIP) to capture their in vivo binding to target RNAs. LIN28A-binding RNAs were identified in a mouse embryonic stem cell line using multiple monoclonal and polyclonal antibodies. The result shows that LIN28 preferentially binds to let-7 precursors through GGAG binding motif, which is consistent with our previous results. We also identified that LIN28A binding is enriched in a certain subset of mRNAs. To understand the function of the novel LIN28A-mRNA binding, we carried out ribosome profiling from LIN28A-depleted mouse embryonic stem cells.

overall_design: Examination of mRNA level in embryonic stem cell treated with siRNA for GFP or for Lin28a

first: Jun

last: Cho

first: V

middle: N

last: Kim


title: Molecular sequelae of Nampt Inhibition in Human Multiple Myeloma cell line

city: Boston

first: Michele

last: Cea

address: 450 Brookline Av

department: Medical oncology

institute: Dana farber Cancer institute

summary: Evaluation of specific coordinated pattern of transcriptional events consistent with anti-myeloma activity of FK866 (chemical Nampt inhibitor)

overall_design: 3 samples were analyzed using as control the untreated cells. Treated cells were cultured in presence of FK866 at concentration of 10nM for 6 and 24 hours.

first: Antonia

last: Cagnetta


title: Notch is active in Langerhans Cell Histiocytosis and confers pathognomonic features on dendritic cells.

status: Public on Oct 24 2012

city: Vienna

first: Maximilian

last: Kauer

address: Zimmermannplatz 10

department: Molecular Biology

country: Austria

institute: CCRI, St.Anna Children Cancer Research Institute

summary: Langerhans cell histiocytosis (LCH) is a disease characterized by the accumulation of eponymous CD1a+ Langerin+ Langerhans-cell (LC)-like dendritic cells (DC) of largely unknown origin. Here we have performed comparative transcriptome analysis of highly purified CD207+/CD1a+ Langerhans cell histiocytosis (LCH) cells derived from different locations and disease courses and three major human dendritic cell lineages: epidermal Langerhans cells, myeloid dendritic cells (mDC1) and plasmacytoid dendritic cells (pDC) in order to investigate the relationship between LCH cells and naturally occurring dendritic cells. Data obtained indicate that LCH cells form a distinct DC entity. Furthermore, we have identified transcripts that are uniquely expressed by LCH cells in comparison to LC, mDC1, and pDC, and induce LCH-specific features in human DC.

overall_design: Primary cells were isolated from peripheral blood (mDC1 and pDC), skin (epidermal Langerhans cells) and  CD207+/CD1a+ Langerhans cell histiocytosis (LCH) cells derived from different locations. RNA was isolated from these cells ex vivo.

first: Caroline

last: Hutter

first: Ernst

last: Kriehuber


title: PTP1B deficiency effect on mammary gland development and differentiation

status: Public on Oct 23 2012

city: Basel

first: Tim

last: Roloff

address: Maulbeerstrasse 66

department: Functional Genomics

institute: FMI

summary:
Analysis of protein tyrosine phosphatase 1B (PTP1B) deficient mammary glands from nulliparous mice at estrous and pregnancy day 3, 7, 10 and 15. We used a genetically ablated PTP1B mouse model to gain a deeper knowledge of the role PTP1B plays in mammary gland development and to define the mechanism regulated by this phosphatase.
Results provide insight into the role of PTP1B in mammary gland development and differentiation.

overall_design: Mouse mammary glands were isolated from PTP1B -/- and PTP1B +/+ nulliparous mice at estrous and pregnancy day 3, 7, 10 and 15 for RNA extraction and hybridization on Affymetrix microarrays.

first: E

last: Milani

first: T

first: S

last: Thiry

first: M

last: Bentires-Alj


title: Microarray analysis of GFP-SAS cells treated with siAURKA and MLN8237

city: Toon

first: Hiroshi

last: Tanaka

state: Ehime

address: 454 Shitsukawa

department: Oral and Maxillofacial Surgery

institute: Ehime University

summary: Knockdown of AURKA by siAURKA and treatment with MLN8237 markedly inhibit the growth of GFP-SAS cells. We investigated the molecular mechanisms of siAURKA and MLN8237 using the Affymetrix GeneAtlasTM System.

overall_design: Using the Affymetrix GeneAtlas System, we compared gene expression profiles of GFP-SAS cells treated with siAURKA, siNon-target (siNT), MLN8237, or DMSO.

first: Koh-ichi

last: Nakashiro


title: To elucidate the role of estradiol- 17β (E2) in the regulation of corpus luteum function

city: BANGALORE

first: SUDESHNA

last: TRIPATHY

state: KARNATAKA

address: NEW BIOLOGICAL SCIENCES BUILDING

department: MOLECULAR REPRODUCTION, DEVELOPMENT AND GENETICS

institute: INDIAN INSTITUTE OF SCIENCE

summary: Corpus luteum (CL) is a transient endocrine tissue formed from the remnants of the ovarian follicle after ovulation. In response to gonadotropin surge, the ovulating follicle undergoes dramatic changes in expression of genes and differentiation of follicular cells into luteal cells. In several species, of the several genes that are down- regulated post ovulation, Cyp19A1 that codes for aromatase, essential for biosynthesis of estradiol- 17β (E2), also get down- regulated but appears to get up- regulated at later time points in the estrous cycle to have critical role in E2 secretion. In primates and rodents, higher expression and higher E2 levels has been observed in CL. Surprisingly, in the recently carried out gene expression profiling of PGF2α- induced luteolysis studies in the bovine species [GSE27961], it was observed that expression of one of the earliest genes that was down- regulated was Cyp19A1 in the CL. However, the specific role of E2 in the regulation of CL function remains poorly defined. Thus, in the present study, efforts were made to examine the temporal changes in the global gene expression profile in the CL of pregnant rats after treatment with aromatase inhibitor (AI), Anastrozole, and E2 supplementation. The results obtained will further expand our knowledge on E2 target/responsive genes and the basic mechanism(s) that regulates the CL function.  Key words: CL, E2, AI, Gene expression

overall_design: The objective of this study was to identify the effect of E2 deprivation and supplementation on CL function and temporal changes in the transcriptome of pregnant rat CL during day 12 to 16 of pregnancy following E2 deprivation by Anastrozole (AI, Aromatase inhibitor)  treatment in pregnant rats, AI (1mg/ kg bw orally) treatment beginning on day 12 daily for 4 days. In the E2 supplementation experiments, together with AI, the rats were treated with E2 (10µg/ day s.c.). CL tissues were collected on day 12 (no treatment; n=3 animals/ time point), day 16 (vehicle treatment; n=3 animals/ time point), day 16 (AI treatment; n=3 animals/ time point) and day 16 (AI+ E2 treatment; n=3 animals/ time point) to examine gene expression changes associated with E2 deprivation and recovery in the system. Following retrieval of CL from the ovary, corpora lutea were flash frozen in liquid nitrogen and stored at -70oC for the purpose of RNA isolation. The isolated RNA was labelled and hybridized to Affymetrix GeneChip® Rat Gene 1.0 ST arrays as per the manufacturer’s instructions.

last: Tripathy

first: R

last: Medhamurthy


title: Gene expression data from F. tularensis-exposed neutrophils

status: Public on Oct 22 2012

city: Hamilton

first: Addie

last: Whitney

state: MT

address: 903 S 4th St

department: LHBP

institute: NIH/NIAID/RML

summary:
We demonstrated recently that both constitutive and FAS-triggered apoptosis of human neutrophils are profoundly impaired by Francisella tularensis, but how this is achieved is largely unknown.   To test the hypothesis that changes in neutrophil gene expression contribute to this phenotype, we used human oligonucleotide microarrays to identify differentially regulated genes in cells infected with F. tularensis strain LVS compared with uninfected controls.
In order to examine the effect of F. tularensis on the neutrophil transcriptome, we performed microarray expression analysis on human neutrophils treated with F. tularensis subsp. holarctica live vaccine strain (LVS).

overall_design: Polymorphonuclear leukocytes (PMNs) were isolated from the blood of healthy donors.  Control and F. tularensis-exposed PMNs were incubated at 37C for 0, 3, 6, 12, 24, and 48 hours.

first: J

middle: T

last: Schwartz

last: Bhattacharya

middle: D

last: Kobayashi

last: McCracken

first: A

first: F

last: DeLeo

first: L

middle: H

last: Allen


title: Isocitrata Dehydrogenase (IDH) Mutations Promote a Reversible ZEB1/mir-200-Dependent Epithelial Mesenchymal Transition (EMT)

city: Cambridge

first: Joshua

last: Korn

state: MA

address: 250 Mass Ave

institute: Novartis

summary: Mutations in the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a variety of tumor types, resulting in production of the proposed oncometabolite, 2-hydroxyglutarate (2-HG). How mutant IDH and 2-HG alter signaling pathways to promote cancer, though, remains unclear. Additionally, there exist relatively few cell lines with IDH mutations. To examine the effect of endogenous IDH mutations and 2-HG, we created a panel of isogenic epithelial cell lines with either wild-type IDH1/2 or clinically relevant IDH1/2 mutations. Differences were noted in the ability of IDH mutations to cause robust 2-HG accumulation. IDH1/2 mutants that produce high levels of 2-HG cause an epithelial-mesenchymal transition (EMT)-like phenotype, characterized by changes in EMT-related gene expression and cellular morphology. 2-HG is sufficient to recapitulate aspects of this phenotype in the absence of an IDH mutation. In the cells types examined, mutant IDH-induced EMT is dependent on upregulation of the transcription factor ZEB1 and downregulation of the mir-200 family of microRNAs. Furthermore, sustained knockdown of IDH1 in IDH1 R132H mutant cells is sufficient to reverse many characteristics of EMT, demonstrating that continued expression of mutant IDH is required to maintain this phenotype. These results suggest mutant IDH proteins can reversibly deregulate discrete signaling pathways that contribute to tumorigenesis

overall_design: 9 HCT116 isogenic clones with wild-type or IDH1/2 mutations. Samples were analyzed in duplicate.

first: Alexandra

middle: R

last: Grassian

first: Fallon

last: Lin

first: Rosemary

last: Barret

first: Yue

last: Liu

first: Wei

last: Jiang

first: Manav

last: Korpal

first: Holly

last: Astley

first: Daniel

last: Gitterman

first: Thoman

last: Henley

first: Rob

last: Howes

first: Julian

last: Levell

first: Raymond

last: Pagliarini


title: Polyploidization of mesenchymal cells is associated with suppression of the non-coding RNA H19 and with reduced tumorigenicity

status: Public on Oct 21 2012

city: La Jolla

first: Ofer

last: Shoshani

address: 9500 Gilman Drive

institute: Ludwig Institute for Cancer Research

summary: Mesenchymal stromal cells (MSCs) are used extensively in clinical trials; however, the potential for malignant transformation of MSCs has been raised. We examined the genomic stability versus the tumor forming capacity of multiple mouse MSCs. Murine MSCs have been shown to be less stable and more prone to malignant transformation than their human counterparts. A large series of independently isolated MSC populations exhibited low tumorigenic potential under syngeneic conditions, which increased in immune-compromised animals. Unexpectedly, higher ploidy correlated with reduced tumor forming capacity. Furthermore, in both cultured MSCs and primary hepatocytes, polyploidization was associated with a dramatic decrease in the expression of the long non-coding RNA H19. Direct knockdown of H19 expression in diploid cells resulted in acquisition of polyploid cell traits. Moreover, artificial tetraploidization of diploid cancer cells led to a reduction of H19 levels, as well as to an attenuation of the tumorigenic potential. Polyploidy might therefore serve as a protective mechanism aimed at reducing malignant transformation through the involvement of the H19 regulatory long non-coding RNA.

overall_design: Overall, six different samples are compared, three diploid biological replicate diploid MSCs, and three tetraploid biological replicate MSCs.

first: Hassan

last: Massalha

first: Dena

last: Leshkowitz

first: Dov

last: Zipori


title: The effects of NAC on gene expression in Nkx3.1-/- mouse prostate

city: Nashville

first: Philip

last: Anderson

department: Pathology

institute: Vanderbilt University

summary: We tested the effects of the antioxidant NAC (N-Acetyl-Cysteine) on gene expression in Nkx3.1-deficient mouse prostate.

overall_design: Mice that were homozygous null for Nkx3.1 were given NAC or plain water ad libidum for 13 weeks after weaning. Prostates were collected, RNA was harvested and reverse transcribed, and cDNA was hybridized to Affy Mouse Gene 1.0 ST microarrays.

first: Erin

middle: E

last: Martinez

first: Sarki

last: Abdulkadir


title: Genome-wide characterization of PhoB binding profile in Escherichia coli

city: Taipei

first: Chi

last: Yang

address: No.155, Sec.2, Linong Street

department: Institute of BioMedical Informatics

institute: National Yang-Ming University

type: Genome binding/occupancy profiling by genome tiling array

summary: This SuperSeries is composed of the SubSeries listed below.

platform_organism: Escherichia coli str. K-12 substr. MG1655

overall_design: Refer to individual Series

first: Tzu-Wen

last: Huang

first: Shiau-Yi

last: Wen

first: Chun-Yang

last: Chang

first: Shih-Feng

last: Tsai

first: Whei-Fen

last: Wu

first: Chuan-Hsiung


title: Genome-wide expression study of the responses of murine NK cells and dendritic cell subsets after poly(I:C) injection

status: Public on Oct 17 2012

city: marseille

first: Thien-Phong

last: Vu Manh

address: 163 avenue de Luminy

institute: CIML

summary:
The injection of the pathogen-associated molecular pattern Polyinosinic-polycytidylic acid (poly(I:C)) leads to the activation of various immune cells, including dendritic cells (DCs) and Natural Killer (NK) cells. This activation is  due to different innate cytokines produced early after injection, in particular IFN-I. The objective of the study was to compare the pattern of expression of IFN-I stimulated genes between DC and NK cells.
The project focused on a specific subset of conventional DC, CD8a DC, which responsiveness to IFN-I determines the capacity to activate CD8 T cells by cross-presentation of exogenous antigens.  To identify the responses to IFN-I selectively induced in CD8a+ DC, we compared their gene expression profile to that of NK cells, using gene chips, before and after poly(I:C) stimulation.

overall_design: This study includes data from CD8a+ cDCs and NK cells purified by flow cytometry from the spleen of WT C57BL/6 mice, under steady-state conditions or 3 hours after administration of 100 ug  poly(I:C) by intravenous injection. Two independent replicates were made for each cell type.

first: K

last: Crozat

first: TP

first: M

last: Dalod


title: Expression data of transduced mouse glioblastomas

status: Public on Oct 18 2012

city: Charlottesville

first: Eugene

last: Ke

state: Virginia

address: P.O. Box 800734, 1340 Jefferson Park Avenue

department: MIC

institute: University of Virginia

summary: Transgenic GFAP-, NES-, and SYN- CRE mice were injected with a lenti-viral construct containing a floxed RFP directly upstream of a cassette containing si-p53, GFP, and mutant HRAS. Tumors arising from the various CRE tissue specific promoters and differing injections sites were compared to normal hippocampus and cortex.

overall_design: RNA was isolated from dissected tumors and applied to microarray anaylsis using Affymetrix Mouse Gene 1.0 ST Arrays according to manufactures instructions

first: Dino

last: Friedmann-Morvinski

first: Inder

last: Verma


title: Genome-wide characterization of PhoB binding profile in Escherichia coli (gene expression data)

summary: Chromatin immunoprecipitation was combined with high-density tiling array (ChIP-chip) and gene expression microarray to reveal the adaptive responses of Escherichia coli to phosphate starvation. The first sketch of the genome-wide distribution of PhoB binding profile was unveiled and 43 regions were identified as the PhoB binding regions. The presence of a significant common motif in these binding regions allowed us to reconstruct the PhoB binding pattern. By comparing the ChIP-chip and microarray datasets, we were also able to identify genes directly or indirectly affected through PhoB regulation. Nineteen out of the 287 differentially expressed genes in the presence and absence of PhoB activity were considered as the genes directly regulated by PhoB. The adaptive responses affected through PhoB regulation are discussed and these responses involve in several important biological functions including transcriptional regulation, transportation, membrane component arrangement, sigma factor modulation and DNA replication inhibition.

overall_design: Under phosphate starvation condition, the gene expression profiles from MG1655 and its PhoB knock-out isogenetic strain are compared to identify the PhoB affected genes.


title: Distinct gene expression profiles of viral- and non-viral associated Merkel cell carcinoma revealed by transcriptome analysis

first: Paul

last: Harms

address: 1301 Catherine

type:
Expression profiling by array
Third-party reanalysis

summary:
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor with high mortality rates. Merkel cell polyomavirus (MCPyV), identified in the majority of MCC, may drive tumorigenesis via viral T antigens.   However, mechanisms underlying pathogenesis in MCPyV-negative MCC remain poorly understood. To nominate genes contributing to pathogenesis of MCPyV-negative MCC, we performed DNA microarray analysis on 30 MCCs. MCPyV status of MCCs was determined by PCR for viral DNA and RNA. 1593 probe-sets were differentially expressed between MCPyV-negative and -positive MCC, with significant differential expression defined as at least 2-fold change in either direction and p-value of ≤ 0.05. MCPyV-negative tumors showed decreased RB1 expression, whereas MCPyV-positive tumors were enriched for immune response genes. Validation studies included immunohistochemistry demonstration of decreased RB protein expression in MCPyV-negative tumors and increased peritumoral CD8+ T lymphocytes surrounding MCPyV-positive tumors. In conclusion, our data suggest that loss of RB1 expression may play an important role in tumorigenesis of MCPyV-negative MCC. Functional and clinical validation studies are needed to determine whether this tumor suppressor pathway represents an avenue for targeted therapy.
We used microarrays to characterize global gene expression patterns related to Merkel cell polyomavirus status in Merkel cell carcinoma.  Furthermore, we compared Merkel cell carcinoma to less aggressive primary cutaneous carcinomas.

overall_design:
We utilized flash-frozen tumor tissue from primary Merkel cell carcinomas, metastatic Merkel cell carcinomas, primary cutaneous squamous cell carcinomas, and basal cell carcinomas. Merkel cell carcinoma cell lines, which represent a pure population of tumor cells, were also included. Merkel cell polyomavirus status was determined at the DNA and RNA level using multiple primers for viral T-antigen and capsid protein sequences.
This Series represents two analyses - one with new Samples normalized together, and another with some of the new Samples re-normalized with Samples previously submitted under Series GSE13355.  The latter group contain 'renormalized' in the titles.

first: Christopher

last: Bichakjian


title: Expression data in inguinal adipose tissue at different circadian times

city: Philadelphia

first: Georgios

middle: K

last: Paschos

state: PA

address: 10-102 Translational Research Center, 3400 Civic Center Boulevard, Building 421

institute: University of Pennsylvania, School of Medicine

summary: Peripheral circadian clocks regulate many aspects of physiology. In this study we deleted the core circadian clock component Bmal1 specifically in mouse adipocytes in order to study the role of the adipocyte clock in energy homeostasis and body weight. We used microarrays to indentify changes in gene expression in the adipose tissue of mice lacking a functional adipocyte circadian clock and identified a small  number of up- and down- regulated genes.

overall_design: Adipose tissues were isolated from inguinal adipose fat pads at four different times of the diurnal cycle under constant darkness (circadian time, CT) for RNA extraction and hybridization on Affymetrix microarrays. Adipocyte-specific Bmal1 KO (Ad-Bmal1-/-) and control mice were used for isolation of tissues at CT0, CT6, CT12, CT18 where CT0 the beginning of the subjective day.

first: Garret

last: FitzGerald


title: Expression data from WT DN3, TCF-1-deficient DN3 thymocytes, and T cell lymphomas in TCF-1-deficient animals.

city: Nutley

first: Hai-Hui

last: Xue

state: NJ

address: 111 Ideation Way

department: Center for Discovery and Innovation

institute: Hackensack University Medical Center

summary:
TCF-1 is an HMG family transcription factor which is known to be critical for T cell development. We discovered that it has a unique role in suppressing malignant transformation of developing thymocytes at early stages. We identified ID2 and LEF-1 as key TCF-1 target genens in tumor suppression.
We used microarrays to detect gene expression changes in WT and TCF-1 deficient DN3 thymocytes as well as T cell lymphoma cells developed in TCF-1 KO mice.

overall_design: DN3 thymocytes were directly sorted from WT or TCF-1 KO mice. T cell lymphoma blast cells were also sorted from TCF-1 KO mice that developed the disease. RNA was extracted and hybridized to GeneChip Mouse GENE 1.0 ST arrays (Affymetrix).

first: Shuyang

last: Yu


title: Gene expression data from glioblastoma tumor samples

status: Public on Oct 16 2012

city: Heidelberg

first: Marcel

last: Kool

address: Im Neuenheimer Feld 580

department: Pediatric Neuro Oncology

institute: German Cancer Research Center

summary:
Glioblastoma (GBM) is an incurable brain tumor carrying a dismal prognosis, which displays considerable heterogeneity. We have recently identified recurrent H3F3A mutations affecting two critical positions of histone H3.3 (K27, G34) in one-third of pediatric GBM. Here we show that each of these H3F3A mutations defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and are mutually exclusive with IDH1 mutation (characterizing a CpG-Island Methylator Phenotype (CIMP) subgroup). Three further epigenetic subgroups were enriched for hallmark genetic events of adult GBM (EGFR amplification, CDKN2A/B deletion) and/or known transcriptomic signatures. We also demonstrate that the two H3F3A mutations give rise to GBMs in separate anatomic compartments, with differential regulation of OLIG1/2 and FOXG1, possibly reflecting different cellular origins.
To further dissect the biological differences between epigenetic glioblastoma subgroups, we looked at the transcriptomic profiles of glioblastoma samples.

overall_design: 46 glioblastoma samples from patients of various ages were selected for RNA extraction and hybridization on Affymetrix Affymetrix Human Genome U133 Plus 2.0 Arrays.

first: Dominik

last: Sturm

first: Hendrik

last: Witt

first: Volker

last: Hovestadt

first: Dong-Anh

last: Khuong Quang

first: Christoph

last: Plass

first: Nada

last: Jabado

first: Stefan

last: Pfister


title: Gene expression profile of human T-ALL cell line KOPTK1 treated with vehicle or PD 0332991

first: Takaomi

last: Sanda

address: 450 Brookline Ave

institute: Dana-Farber Cancer Institute

summary: D-cyclins represent components of cell cycle machinery. To test the efficacy of targeting D-cyclins in cancer treatment, we engineered mouse strains which allow acute and global ablation of individual D-cyclins in a living animal. Ubiquitous shutdown of cyclin D1 or inhibition of cyclin D associated kinase activity in mice bearing ErbB2-driven mammary carcinomas halted cancer progression and triggered tumor-specific senescence, without compromising the animals' health. Ablation of cyclin D3 in mice bearing T-cell acute lymphoblastic leukemias (T-ALL) triggered tumorspecific apoptosis. Such selective killing of leukemic cells can be also achieved by inhibiting cyclin D associated kinase activity in mouse and human T-ALL models. Hence, contrary to what one might expect from ablation of a cell cycle protein, acute shutdown of a D-cyclin leads not only to cell cycle arrest, but it also triggers tumor cell senescence or apoptosis, and it affects different tumor types through distinct cellular mechanisms. Inhibiting cyclin D-activity represents a highly-selective anticancer strategy which specifically targets cancer cells without significantly affecting normal tissues.

overall_design: A human T-ALL cell line KOPTK1 cells were cultured in the presence of the CDK4/6 inhibitor PD 0332991 (PD; 1 microM) or vehicle (VO) for 48 hrs. Experiment was done in biological triplicate. A total of 6 RNA samples (3 vehicle treated and 3 PD 0332991 treated samples) were used for microarray expression analysis.

first: Yoon

last: Choi

first: Xiaoyu

last: Li

first: Per

last: Hydbring

first: Joanna

last: Stefano

first: Amanda

last: Christie

first: Sabina

last: Signoretti

first: Thomas

last: Look

first: Andrew

last: Kung

first: Harald

last: von Boehmer

first: Piotr

last: Sicinski


title: DNA methylation profiling in breast cancer discordant identical twins

city: L'Hospitalet de Llobregat

first: Manel

last: Esteller

address: Hospital Duran i Reynals Av. Gran Via s/n km, 2.7

department: PEBC

institute: IDIBELL

summary: We obtained a comprehensive DNA methylation profile of 15 breast cancer discordant twins, using the high resolution Infinium HumanMethylation450 BeadChip platform (450K, Illumina), previously established to reliably detect methylation changes of more than 450,000 CpG sites. To provide insight into the temporal and causal relationships and predictive potential, samples from breast cancer patients before (7) and after diagnosis (8) were also analyzed. Using whole blood from 15 twin pairs discordant for breast cancer and high-resolution (450k) DNA methylation analysis we identified 403 differentially methylated CpG sites including known and novel potential breast cancer genes.

overall_design: 30 Samples

first: Holger

last: Heyn


title: Transcriptional perturbations caused by SV40 large T antigen and its fragments

status: Public on Oct 26 2012

city: Tucson

first: Megha

last: Padi

state: AZ

address: 1071 East Lowell St.

department: Molecular and Cellular Biology

institute: University of Arizona

summary: The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains that contribute to the viral life cycle, including the DNA binding and helicase domains.  In addition, the LT the C-terminal region is required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells and identified interacting cellular proteins and performed expression profiling.  LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes.

overall_design: To examine transcriptome perturbations directly in human cells, we generated expression constructs of each LT fragment. Full length and truncated LT containing N-terminal HA and FLAG epitope tags were expressed from the pMSCV retroviral vector and introduced into U-2 OS cells. Total RNA was isolated from three biological replicate U-2 OS stable cell lines and gene expression was assayed on Affymetrix Human Gene U133 Plus 2.0 arrays.

first: Debrah

last: Fine

first: Orit

last: Rozenblatt-Rosen

first: James

last: DeCaprio


title: DNA damage and eIF4G1 in breast cancer cells reprogram translation for survival and DNA repair mRNAs

city: LYON

first: Jiri

last: ZAVADIL

state: Other

address: 150 COURS ALBERT THOMAS

institute: IARC WHO

summary:
The cellular response to DNA damage is mediated through multiple pathways that regulate and coordinate DNA repair, cell cycle arrest  and cell death. We show that the DNA damage response (DDR) induced by ionizing radiation (IR) is coordinated in breast cancer  cells by selective mRNA translation mediated by high levels of translation initiation factor eIF4G1. Increased expression of eIF4G1,  common in breast cancers, was found to selectively increase translation of mRNAs involved in cell survival and the DDR, preventing  autophagy and apoptosis (Survivin, HIF1α, XIAP), promoting cell cycle arrest (GADD45a, p53, ATRIP, Chk1) and DNA repair (53BP1,  BRCA1/2, PARP, Rfc2-5, ATM, MRE-11, others). Reduced expression of eIF4G1, but not its homolog eIF4G2, greatly sensitizes cells to  DNA damage by IR, induces cell death by both apoptosis and autophagy, and significantly delays resolution of DNA damage foci  with little reduction of overall protein synthesis. While some mRNAs selectively translated by higher levels of eIF4G1 were found  to use internal ribosome entry site (IRES)-mediated alternate translation, most do not. The latter group shows significantly reduced  dependence on eIF4E for translation, facilitated by an enhanced requirement for eIF4G1. Increased expression of eIF4G1 therefore  promotes specialized translation of survival, growth arrest and DDR mRNAs that are important in cell survival and DNA repair  following genotoxic DNA damage.
The purpose of this study was to identify mRNAs that are selectively increased in translation by high levels of the initiation factor eIF4G1, which occurs in many advanced human cancers,  in response to DNA damage caused by ionizing radiation,

overall_design: Polysome isolation was performed by separation of ribosome-bound mRNAs in sucrose gradients.  Beckman Ultra-Clear centrifuge tubes were loaded with 5.5 ml of 50% sucrose in low salt buffer (LSB: 200 mM Tris pH7.4 in DEPC H2O, 100 mM NaCl, 30 mM MgCl2) with 1:1000 RNasin (Fermentas) and 100 μg/mL cycloheximide (CHX) in ethanol and incubated at 4°C horizontally overnight.  Media was removed from cell cultures, replaced with media containing 100 μg/mL CHX, cells incubated at 37°C for 10 min to halt protein synthesis, and trypsinized in trypsin/EDTA containing 100 μg/mL CHX.  Cells were washed twice in PBS containing CHX, RNasin and Roche complete EDTA-free protease inhibitor tablet, lysed in LSB with CHX and RNasin.  Lysates were added to a Dounce homogenizer and incubated on ice for 3 min before addition of Triton detergent buffer (1.2% Triton N-100, 0.2M sucrose in LSB) and homogenization.  Samples were transferred to cold sterile Eppendorf centrifuge tubes and centrifuged at 13,000 x RPM for 10 min at 4°C.  Post-nuclear supernatants were transferred to centrifuge tubes containing 100 μL Heparin solution (10 mg/mL heparin, 1.5M NaCl in LSB) with RNasin and CHX, applied to a sucrose gradient.  Gradients were centrifuged at 36K RPM at 4°C for 2 h, and supernatants recovered with an ISCO-UV fractionator.  Samples were recovered into Eppendorf centrifuge tubes containing 40 μL RNase-free 0.5M EDTA and kept on ice.  One volume acidic phenol-chloroform was added to each sample, which were then mixed and centrifuged at 10,000 x g for 15 min.  The acidic phenol-chloroform extraction was repeated with the aqueous phase, which was then extracted twice via chloroform extraction.  RNA was precipitated at -20°C overnight by addition of isopropanol with 0.1 vol NaOAc, pH5.2.  The following day, RNA pellets were recovered by centrifugation, washed with 70% ethanol, air-dried and resuspended in sterile H2O.  RNA from fractions was then pooled based on their relative rate of translation, with fractions containing 4 or more ribosomes considered heavily translated and used for gene chip analysis.  The RNA quality was examined via the Agilent Technologies kit.

first: Michelle

last: Badura

first: Steve

last: Braunstein

last: Zavadil

first: Robert

last: Schneider


title: Methylation data from glioblastoma tumor samples

first: Dominik

last: Sturm

address: Im Neuenheimer Feld 280

summary: Glioblastoma (GBM) is an incurable brain tumor carrying a dismal prognosis, which displays considerable heterogeneity. We have recently identified recurrent H3F3A mutations affecting two critical positions of histone H3.3 (K27, G34) in one-third of pediatric GBM. Here we show that each of these H3F3A mutations defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and are mutually exclusive with IDH1 mutations (characterizing a CpG-Island Methylator Phenotype (CIMP) subgroup). Three further epigenetic subgroups were enriched for hallmark genetic events of adult GBM (EGFR amplification, CDKN2A/B deletion) and/or known transcriptomic signatures. We also demonstrate that the two H3F3A mutations give rise to GBMs in separate anatomic compartments, with differential regulation of OLIG1/2 and FOXG1, possibly reflecting different cellular origins. We identified six epigenetic and biological GBM subgroups displaying distinct global DNA methylation patterns, which harbor unique hotspot mutations, DNA copy-number alterations, and transcriptomic patterns.

overall_design: We investigated a subset of childhood (n=59) and adult GBMs (n=77) using the Illumina 450k methylation array. Six non-neoplastic brain tissue samples are included as controls.

first: Hendrik

last: Witt

first: Volker

last: Hovestadt

first: Dong

last: Khuong Quang

first: David

last: Jones

first: Carolin

last: Konermann

first: Elke

last: Pfaff

first: Martje

last: Tönjes

first: Martin

last: Sill

first: Sebastian

last: Bender

first: Marcel

last: Kool

first: Marc

last: Zapatka

first: Natalia

last: Becker

first: Manuela

last: Zucknick

last: Hielscher

first: Xiao

middle: Y

last: Liu

first: Adam

last: Fontebasso

first: Marina

last: Ryzhova

first: Steffen

last: Albrecht

first: Karine

last: Jacob

first: Marietta

last: Wolter

last: Ebinger

middle: U

last: Schuhmann

first: Timothy

last: van Meter

first: Michael

middle: C

last: Frühwald

last: Hauch

first: Arnulf

last: Pekrun

first: Bernhard

last: Radlwimmer

first: Tim

last: Niehues

first: Gregor

last: von Komorowski

first: Matthias

last: Dürken

first: Andreas

last: Kulozik

first: Jenny

last: Madden

last: Donson

first: Nicholas

last: Foreman

first: Rachid

last: Drissi

first: Maryam

last: Fouladi

first: Wolfram

last: Scheurlen

last: von Deimling

first: Camelia

last: Monoranu

first: Wolfgang

last: Roggendorf

first: Christel

last: Herold-Mende


title: Blood mRNA expression signatures derived from unsupervised analyses identify prostate cancers with poor outcome

status: Public on Oct 15 2012

city: Sutton

first: Ian

last: Giddings

state: Surrey

address: 15 Cotswold Road

department: Section of Molecular Carcinogenesis

country: United Kingdom

institute: Institute of Cancer Research

summary:
Background: Inter-patient prostate cancer (PrCa) heterogeneity results in highly variable patient outcomes. Multi-purpose biomarkers to dissect this heterogeneity are urgently required to improve treatment and accelerate drug development in PrCa. Circulating biomarkers are most practical for evaluating this disease. We pursued the analytical validation and clinical qualification of blood mRNA expression arrays.
Methods: Whole blood samples were collected into PaxGeneTM tubes from PrCa patients: 31 good prognosis patients selected for active surveillance (AS) and 63 advanced castration resistant PrCa (CRPC) patients. RNA was extracted, amplified, biotinylated, and hybridised to Affymetrix U133plus2 microarrays and analysis of genome-wide expression profiles were analysed using Bayesian Latent Process Decomposition (LPD).
Findings: LPD analysis of the mRNA expression data divided the evaluable patients (n=94) into 4 separate groups. LPD1 and LPD2 consisted almost entirely of CRPC patients (14/14; 17/18); LPD3 (15/31) and LDP4 (12/21) comprised both AS and CRPC. Ten patients were unclassifiable by LPD analysis. LPD1 CRPC patients had significantly poorer overall survival (median 10.7 months, CI-95% 4.2-17.2) than CRPC patients in LPD2 to 4 (median 26.5 months, CI-95% 18.1-34.9, p=0.00007). LPD 1 membership remained the strongest prognostic factor in a multivariate analysis (HR 5.0, CI-95% 2.1-11.9, p=0.0002). Gene signatures in the poor prognosis LPD group 1 were associated with increased CD71+ early erythroid cells and decreased B-cell and T-cell immune response. A 9-gene signature, that was validated by RT-PCR studies, classified patients as group LPD 1 with a very low misclassification rate (1.2%).
Interpretation: Poor PrCa outcome can be predicted using gene expression signatures from whole blood and merits further evaluation in predictive and pharmacodynamic biomarker studies for novel anticancer drugs including immune therapies.

overall_design: 107 blood samples were collected in paxgene tubes from 94 prostate cancer patients (31 good prognosis & 63 advanced castration resistant PrCa). Replicates include 9 biological replicates and four technical replicates

first: David

last: Olmos

first: Daniel

last: Brewer

first: Jeremy

last: Clark

first: Chris

last: Parker

first: Gerhardt

last: Attard

first: Shahneen

last: Sandhu

first: Alison

last: Reid

first: Lorraine

last: Barwell

first: Elena

last: Castro

first: Nikhil

middle: B

last: Oomen

first: Suzanne

last: Carreira

first: Charles

middle: G

last: Drake

first: Gino

last: Miele

first: Robert

last: Jones

first: Colin

middle: S

last: Cooper

first: Johann

last: de Bono


title: Overexpression of NUCKS1 in colorectal cancer correlates with recurrence after curative surgery (gene expression analysis)

city: Bunkyo-ku

first: Kaoru

last: Mogushi

state: Tokyo

address: 2-1-1 Hongo

department: Intractable Disease Research Center

institute: Juntendo University

summary:
Purpose: The purpose of this study is to identify a novel biomarker related with distant metastases of colorectal cancer (CRC).
Experimental Design: We investigated mRNA expression profiles in 115 patients with CRC using an Affymetrix Gene Chip, and copy number profiles in 122 patients with CRC using an Affymetrix DNA Sty array. Genes in common between copy number and expression data were extracted as candidate genes. We analyzed the mRNA expression of candidate gene by quantitative reverse transcription polymerase chain reaction (RT-PCR) in 86 patients as a validation study. Furthermore, we analyzed the protein expression of candidate gene by immunohistochemical study in 269 patients, and investigated the relationship between protein expression and clinicopathologic features.
Results: By the combination of copy number analysis and gene expression analysis, We extracted 2 candidate genes related with distant metastases of CRC. Several reports show that NUCKS1, one of candidate genes, is overexpressed in several cancer tissues. But a study about the relationship between NUCKS1 and CRC is none. The mRNA expression of NUCKS1 in cancer tissues was significantly higher than those in normal tissues. Overexpression of NUCKS1 protein was associated with significantly worse　relapse-free survival of CRC. Overexpression of NUCKS1 protein was an independent risk factor for recurrence of CRC.
Conclusion: The overexpression of NUCKS1 would be a new biomarker predicting recurrence after colorectal surgery.

overall_design:
Total 115 microarray datasets obtained from LCM samples of colorectal cancer patients were normalized using robust multi-array average (RMA) method under R statistical software version 2.12.1 together with BioConductor package. The normalized gene expression levels were presented as log2-transformed values by RMA, and 62 control probe sets were removed for further analysis.

This submission represents the transcriptome component of the study.

first: Akifumi

last: Kikuchi

first: Toshiaki

last: Ishikawa

first: Satoru

last: Iida

first: Megumi

last: Ishiguro

first: Hiroshi

last: Mizushima

first: Hiroyuki

last: Uetake

last: Tanaka

first: Kenichi

last: Sugihara


title: Expression data from ALK over-expressed MCF-7 clones and control clones

city: Houston

first: Annie

middle: Z

last: Luo

state: Texas

address: 1901 East Road 4SCR3.1004

department: Experimental Therapeutics

institute: M D Anderson Cancer Center

summary: To evaluate the function of ALK in breast cancer, we enforcing expressed full length wild type ALK in the parental MCF-7 breast cancer cell line that we have established in previous studies have a very low invasive capacity, do not form tumor emboli nor do they invade into the dermal lymphatics when grown as xenografts.

overall_design: Whole unbiased transcriptome analysis were performed using ALK over-expressed MCF-7 clones and control clones. Pathway mapping revealed that the presence of ALK induced up and down regulation changes of series of genes within several canonical signal pathway.


title: Gene expression profiling of two DLBCL cell lines upon shRNA mediated knockdown of  EZH2

status: Public on Oct 12 2012

city: Collegeville

first: Gopinath

last: Ganji

address: 1250 South Collegeville Road

institute: GSK

summary:
We studied transcriptional changes by Affymetrix human microarrays in 2 DLBCL cell lines as a result of shRNA mediated knockdown of EZH2.
In eukaryotes, epigenetic post-translational modification of histones is critical for regulation of chromatin structure and gene expression. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) and is responsible for repressing target gene expression through methylation of histone H3 on lysine 27 (H3K27). Over-expression of EZH2 is implicated in tumorigenesis and correlates with poor prognosis in multiple tumor types. Recent reports have identified somatic heterozygous mutations of Y641 and A677 residues within the catalytic SET domain of EZH2 in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The Y641 residue is the most frequently mutated residue, with 22% of GCB (Germinal Cell B-cell) DLBCL and FL harboring mutations at this site. These lymphomas exhibit increased H3K27 tri-methylation (H3K27me3) due to altered substrate preferences of the mutant enzymes. However, it is unknown whether direct inhibition of EZH2 methyltransferase activity alone will be effective in treating lymphomas carrying activating EZH2 mutations.  Herein, we demonstrate that GSK126, a potent, highly-selective, SAM-competitive, small molecule inhibitor of EZH2 methyltransferase activity, decreases global H3K27me3 levels and reactivates silenced PRC2 target genes. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and dramatically inhibits the growth of EZH2 mutant DLBCL xenografts in mice. Together, these data demonstrate that pharmacological inhibition of EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma.

overall_design: Pfeiffer and KARPAS-422 cells were treated with either shRNA targeting EZH2 (shEZH2) or a non targeting control (shNTC) for 10 days.

first: Michael

last: McCabe

first: Caretha

middle: L

last: Creasy


title: Profiling of ovarian tumour and benign lesions

city: London

first: Ed

last: Curry

address: Hammersmith Hospital, Du Cane Road

institute: Imperial College London

summary: Investigation of malignancy-associated expression of gene sets based on ovarian tumour histone modification status.

overall_design: A single serous epithelial ovarian tumour (which was assayed using ChIP-seq to determine histone modification profiles; SRA059358) was profiled using the HGU133 plus 2 GeneChip, along with 8 benign ovarian lesions (1 serous cyst, 3 serous cystadenomas and 4 serous cystadenofibromas) for comparison. Expression levels of genes marked in the tumour with particular histone modifications were compared between the tumour and the benign samples.

first: Edward

middle: W

first: Nadine

last: Chapman-Rothe

last: Brown


title: Gene expression profiling of EZH2 mutant and wild type DLBCL cell lines treated with EZH2 inhibitor

summary:
We studied transcriptional changes by Affymetrix human microarrays in DLBCL cell lines as a result of treatment with GSK126, a potent, highly-selective, SAM-competitive, small molecule inhibitor of EZH2
In eukaryotes, epigenetic post-translational modification of histones is critical for regulation of chromatin structure and gene expression. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) and is responsible for repressing target gene expression through methylation of histone H3 on lysine 27 (H3K27). Over-expression of EZH2 is implicated in tumorigenesis and correlates with poor prognosis in multiple tumor types. Recent reports have identified somatic heterozygous mutations of Y641 and A677 residues within the catalytic SET domain of EZH2 in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The Y641 residue is the most frequently mutated residue, with 22% of GCB (Germinal Cell B-cell) DLBCL and FL harboring mutations at this site. These lymphomas exhibit increased H3K27 tri-methylation (H3K27me3) due to altered substrate preferences of the mutant enzymes. However, it is unknown whether direct inhibition of EZH2 methyltransferase activity alone will be effective in treating lymphomas carrying activating EZH2 mutations.  Herein, we demonstrate that GSK126, a potent, highly-selective, SAM-competitive, small molecule inhibitor of EZH2 methyltransferase activity, decreases global H3K27me3 levels and reactivates silenced PRC2 target genes. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and dramatically inhibits the growth of EZH2 mutant DLBCL xenografts in mice. Together, these data demonstrate that pharmacological inhibition of EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma.

overall_design: 10 DLBCL cell lines (7 mutant and 3 wild type EZH2), that were differentially sensitive to GSK126 in proliferation assays, were treated for 72 hours, in duplicate (n=2), with either DMSO (vehicle) or 500nM of GSK126, a potent selective EZH2 inhibitor. EZH2 mutant cell lines are Pfeiffer, KARPAS-422, WSU-DLCL2, SU-DHL-10, SU-DHL-6, DB and SU-DHL-4. EZH2 wildtype cell lines are HT, OCI-LY-19 and Toledo.


title: Gene expression data and CDX1-binding sites in gastric epithelial cells

city: Tokyo

first: Yumiko

last: FUJII

address: 7-3-1, Hongo, Bunkyo-ku

department: Depertment of Microbiology, Graduate School of Medicine

institute: University of Tokyo

summary: To identify the transcriptional targets of CDX1 underlying the metaplastic change, we explored genes affected by ectopic expression of CDX1 in gastric epithelial cells by combining expression microarray and ChIP-chip analyses.

overall_design: CDX1-inducible MKN28 cells, which inducibly express Flag-tagged CDX1 with the use of a tetracycline-regulated Tet-Off System (Clontech), were established from MKN28 human gastric epithelial cells. CDX1-inducible MKN28 cells were cultured for 24 h in the absence or presence of doxycycline (Clontech), a tetracycline analog. We then performed expression microarray and ChIP-chip analyses.

last: Fujii

first: Shuichi

last: Tsutsumi

last: Aburatani


title: Overexpression of NUCKS1 in colorectal cancer correlates with recurrence after curative surgery

first: Kaoru

last: Mogushi

type:
Expression profiling by array
Genome variation profiling by SNP array

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Enhanced immune response of BMDCs pulsed with H9N2 AIV and CpG

status: Public on Oct 11 2012

city: nanjing

first: Jian

last: Lin

state: jiangsu

address: tongwei road N0.1

department: Life Science

country: China

institute: nanjing agricultural university

summary: Dendritic cells (DCs), professional antigen presenting cells, have demonstrated effective in controllingthe initial of innate immune, while CpG could improve the performance of immune system. To explorethe mechanism of CpG enhancing the immune response, we compared different stimulated mouse DCswith systemic approach microarrays. Analysis revealed 1840 differentially expressed genes in H9N2stimulated group, more than 1728 altered genes in inactive H9N2 group. Investigation also proved thatCpG/inactive H9N2 co-stimulation changed 2140 genes, more than that in H9N2 group, strongly demon-strated that CpG improved the performance of inactive H9N2 vaccination. Pathways analysis founded thatDCs response rapid to shift in their maturation state, which involved Toll-like receptor (TLR) pathwaysignificantly. Microarrays results were also verified by qRT-PCR with 14 elected representative genes. Fur-ther analysis proved that co-stimulatory molecules (CD40, CD80, CD86 and MHC-II), regulatory protein(IRF-7 and TRAF-6) and pro-inflammatory cytokines (IL-1, IL-6 and IL-12) were all changed and involvedin DCs maturation. At last we demonstrated TLR signalling pathway in chicken bone marrow-deriveddendritic cells (chBM-DCs) stimulated with CpG. The distinct transcriptional profiles of DCs pulsed withvarious stimuli expanded our understanding of how DCs respond and recognize influenza.

overall_design: The cultured mouse BMDCs were randomly divided into 6 groups (1: control DCs group, 2:CpG stimulated group, 3: H9N2 stimulated group, 4: CpG/H9N2 co-stimulated group, 5: inactivated H9N2 stimulated group, 6: CpG/inactivated H9N2 co-stimulated group). we used microarray to reveal striking transcriptome differences of different stimulated DCs.

first: Yin

last: yan

first: Tao

last: Qin

first: Li

middle: Q

last: Zhu

first: Qing

last: Yu

first: Qian

last: Yang


title: Chromatin H3K27me3/H3K4me3 histone marks define gene sets in high grade serous ovarian cancer that distinguish malignant, tumour sustaining and chemo-resistant ovarian tumour cells.


title: Expression data of A939572 SCD1 inhibitor treated ccRCC cells

city: Jacksonville

first: John

middle: A

last: Copland

state: Florida

address: 4500 San Pablo Rd

department: Cancer Research

country: USA

institute: The Mayo Clinic, Jacksonville FL

summary: Presently, there is a deficiency of effective therapies designed to target clear cell renal cell carcinoma (ccRCC), with poor prognosis resulting in patients with advanced disease. Additionally, there is a lack of molecular factors which can be remedially targeted resulting in tumor specific inhibition, and therefore current therapeutic approaches often produce adverse side effects in patients. We identified that Stearoyl-CoA desaturase 1 (SCD1) was consistently overexpressed in patient ccRCC samples, and further investigation of SCD1 as a potential molecular target for ccRCC intervention utilizing a SCD1 inhibitor (A939572) resulted in tumor specific growth inhibition and induction of cell death. In order to understand the mechanism by which the SCD1 inhibitor mediated its anti-tumor effects, we performed gene array analysis and compared expression patterns between treated and untreated samples.

overall_design: Four established ccRCC cell lines purchased from ATCC were treated with DMSO control versus A939572 over a 24 hour time period. RNA from each group was isolated and sent of for gene array anaylsis. Gene expression data from each individual treatment group was normalized to its respective DMSO contol, and resulting expression patterns associated with drug exposure was compared between the four cell lines.

first: Christina

last: von Roemeling

first: Christopher

last: Kolbert


title: Effect of PRR15 knockdown on human trophoblast cell gene expression

city: Fort Collins

first: Katherine

last: Gates

state: CO

address: 3107 Rampart Rd

department: Biomedical Sciences

institute: Colorado State University

summary:
Proline rich 15 (PRR15) is a small nuclear protein required for normal conceptus development in the sheep.
We used microarrays to assess the changes in the trophoblast transcriptome when PRR15 expression was diminished.

overall_design: The human first-trimester trophoblast cell line, ACH-3P, was infected with control lentivirus expressing no shRNA or lentivirus expressing shRNA to target PRR15 mRNA for degradation, with three biological replicates per treatment.

first: Lindsey

middle: N

last: Goetzmann

first: Jeremy

last: Cantlon

first: Russell

middle: V

last: Anthony


title: Transcriptome in alveolar epithelial type II-like cells differentiated from human lung progenitor cells

city: Sendai

first: Hiroshi

last: Kubo

state: Miyagi

address: 2-1 Seiryomachi, Aobaku

department: Department of Advanced Preventive Medicine for Infectious Disease, and Regenerative Medicine

institute: Tohoku University Graduate School of Medicine

summary: Resident stem/progenitor cells in lungs are important for tissue homeostasis and repair. We isolated human lung progenitor cells and named alveolar epithelial progenitor cells (AEPCs)(Fujino N, et al. 2011. Lab Invest. 91:363). AEPCs have phenotypes of both alveolar epithelial type II (ATII) cells and mesenchymal stem cells. AEPCs had the potential to generate ATII-like cells in vitro. ATII-like cells derived from AEPCs expressed protein and mRNA of pulmonary surfactant, and displayed lamellar bodies containing the surfactants. However, it has not been evaluated whether global gene expression of the ATII-like cells from AEPCs was similar to that of mature ATII cells isolated from human lung tissues. This study demonstrated gene expression profiles of ATII-like cells from AEPCs. In addition, transcriptomes in AEPCs and mature ATII cells were deposited in the GEO website (GSE21095 and GSE29133, respectively).

overall_design: We isolated AEPCs from tissue samples obtained from patients who underwent lung resection at Department of Thoracic Surgery, Tohoku University Hospital. We induced differentiation of AEPCs to ATII-like cells on extracellular matrix with medium containing KGF, cAMP and IBMX, as previously described (Fujino N, et al. 2011. Lab Invest. 91:363). We profiled the gene expression in three different batches of the ATII-like cells. We extracted total RNA from the differentiated cells. This study was approved by the Ethics Committee at Tohoku University School of Medicine. All subjects gave informed consent.

first: Naoya

last: Fujino


title: The Requirement for Cyclin D Function in Tumor Maintenance

city: Boston

first: Takaomi

last: Sanda

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

first: Yoon

middle: J

last: Choi

first: Xiaoyu

last: Li

first: Per

last: Hydbring

first: Joanna

last: Stefano

first: Amanda

last: Christie

first: Sabina

last: Signoretti

first: Thomas

last: Look

first: Andrew

last: Kung

first: Harald

last: von Boehmer

first: Piotr

last: Sicinski