title: Expression data from EZH2 inhibitor treated Non-Hodgkins Lymphoma cell lines

city: Cambridge

first: Yonghong

last: Xiao

address: 400 Technology Square, 4th Floor

department: Biological Sciences

country: USA

institute: Epizyme Inc.

summary:
Mutations within the catalytic domain of the histone methyltransferase (HMT) EZH2 have been identified in subsets of Non-Hodgkin Lymphoma (NHL) patients.  These genetic alterations are hypothesized to confer an oncogenic dependency on EZH2 enzymatic activity in these cancers.  We previously reported the discovery of a potent, selective, S-adenosyl-methionine-competitive and orally bioavailable small molecule inhibitor of EZH2, EPZ-6438.  EPZ-6438 selectively inhibits intracellular lysine 27 of histone H3 (H3K27) methylation in a concentration- and time-dependent manner in both EZH2 wild type and mutant lymphoma cells.  Inhibition of H3K27 trimethylation (H3K27Me3) led to selective cell killing of human lymphoma cell lines bearing EZH2 catalytic domain point mutations.  Treatment of xenograft-bearing mice with EPZ-6438 leads to dose-dependent tumor growth inhibition and eradication of genetically altered NHL with correlative diminution of H3K27Me3 levels in tumors and selected normal tissues.  Mice dosed orally with EPZ-6438 for 28 days remained tumor free for up to 63 day after stopping compound treatment in two EZH2 mutant xenograft models.  These data confirm the dependency of mutant NHL on EZH2 activity and portend the utility of EZH2-targeted drugs for the treatment of these genetically defined cancers.
To identify potential biomarker and gain mechanistic insights in EPZ6438 treated lymphoma, lymphoma cell lines with or without EZH2 Y641 mutation were treated with EPZ6438 at Lowest Cytotoxic Concentration (LCC) and 10xLCC. Transcriptomes were profiled on Affemetrix U133 Plus2 chips. Differentially expressed genes and pathways upon compound treatment were anayzed.

overall_design:
Lymphoma cell lines WSU-DLCL2, SU-DHL6, Pfeiffer, and Karpas422 were treated by EPZ6438 for 2 days, 4 days and 6 days. Treatment doses are LCC and 10xLCC of each cell lines.
KARPAS_422, SUDHL6, and WSU_DLCL2 have the EZH2 Y641 mutation.  PFEIFFER does not have the EZH2 Y641 mutation.

first: Sarah

last: Knutson

first: Heike

last: Keilhack

first: Natalie

last: Warholic

first: Satoshi

last: Kawano

first: Kuan-Chun

last: Huang

first: Yukinori

last: Minoshima


title: Expression data from islets of Pdx1-creLate, control and pregnant mice

status: Public on Feb 14 2014

city: Leuven

first: Leentje

last: Van Lommel

address: Herestraat 49 bus 901

department: Molecular cell biology

country: Belgium

institute: KULeuven

summary:
ABSTRACT: The human growth hormone (hGH) minigene is frequently used in the derivation of transgenic mouse lines to enhance transgene expression. Although this minigene is present in the transgenes as a secondcistron, and thus not thought to be expressed, we found that three commonly used lines, Pdx1-CreLate, RIP-Cre, and MIP-GFP, each expressed significant amounts of hGH in pancreatic islets. Locally secreted hGH binds to prolactin receptors on β cells, activates STAT5 signaling, and induces pregnancy-like changes in gene expression, thereby augmenting pancreatic β cell mass and insulin content. In addition, islets of Pdx1-CreLate mice have lower GLUT2 expression and reduced glucose-induced insulin release and are protected against the β cell toxin streptozotocin. These findings may be important when interpreting results obtained when these and other hGH minigene-containing transgenic mice are used.
Data obtained for the Pdx1-creLate and control samples were compaired to investigate the effect of hGH on the mRNA profile of islets. The data obtained from the islets of pregnant mice was added to the analysis to confirm the pregnacy-like phenotype in the Pdx1-creLate islets. The data of the different days of pregnancy was already described in Schraenen et al. 2010 (PMID: 20886204 and PMID: 20938637).

overall_design: Islets were isolated from Pdx1-creLate, control and pregnant mice for RNA extraction and hybridization on Affymetrix microarrays. For every condition, at least 3 biological replicates were used.

first: Bas

last: Brouwers

first: Anica

last: Schraenen

first: Katleen

last: Lemaire

first: John

middle: M

last: Creemers

first: Frans

last: Schuit


title: Gene expression profiles of SOX17 overexpression in the KYSE170 luciferase cell

status: Public on Feb 12 2014

city: Tainan

first: Yi-Ching

last: Wang

address: No.1, University Road, Tainan 70101, Taiwan, R. O. C.

department: Department of Pharmacology, College of Medicine

country: Taiwan

institute: National Cheng Kung University

summary: SOX17 is a transcriptional factor containing DNA-binding domain HMG box, we hypothesized that there are more genes other than in Wnt singnaling pathway to be transcriptionally regulated by SOX17 in esophageal squamous cell carcinoma.  We performed the GeneChips expression array analyses to reveal more transcriptional target for SOX17.

overall_design: In this study, the esophageal cancer cell line, KYSE170-luc, were transfection with  empty vector and expression plasmids of SOX17 for 12 hours. Total RNA were prepared for microarray assays.

first: I-YING

last: Kuo

first: CHING-CHI

last: Wu

first: YI-CHING


title: Amplification of RANK- and c-Met-mediated signaling promotes metastatic colonization

status: Public on Feb 06 2014

city: LA

first: Sungyong

last: You

state: CA

address: Beverly Blvd 8400

department: Surgery

institute: Cedars-Sinai Medical Center

summary: We found that RANKL, expressed by cancer cells or derived from exogenous sources, consistently induced human prostate, breast, kidney, lung and liver cancer cells to colonize or metastasize to bone in an animal model of cancer bone metastasis. RANK-mediated signaling established a premetastatic niche through a forward feedback loop by inducing RANKL and c-Met expression and downstream signaling via upregulation of master regulator transcription factors regulating EMT (Twist1, Slug, Zeb1, Zeb2), stem cells (Sox2, Myc, Oct3/4 and Nanog), neuroendocrine cells (Sox 9, HIF-1α and FoxA2) and osteomimicry (c-Myc/Max, Sox2, Sox9, HIF1α and Runx2).  Abrogating RANK or its downstream signaling network, c-Myc/Max or c-Met, abolished PCa skeletal metastasis in mice.  We observed that a small number of RANKL-expressing PCa cells can initiate bone and soft tissue metastases by recruiting non-tumorigenic or bystander PCa or host cells from the circulation or at metastatic sites to co-colonize bone.  The recruited bystander PCa cells assume the phenotypes of RANKL-expressing PCa cells by expressing increased c-Met, phosphorylated c-Met and RANKL. RANKL expression at a single cell level in primary PCa tissues predicted disease-specific survival, reflecting the significant role of RANKL-RANK signaling in the development of lethal bone metastasis.

overall_design: Global gene expression analysis perturbed by RANKL in LNRANKL compared to LNNeo cells.

first: Gina

middle: C

last: Chu

first: Michael

middle: R

last: Freeman

first: Leland

middle: W

last: Chung


title: Integrative analysis of histone ChIP-seq and gene expression microarray data using Bayesian mixture models

status: Public on Feb 05 2014

city: Copenhagen N

first: Marie

middle: S

last: Hasemann

address: Ole Maaløes Vej 5

department: Finsen Laboratory

country: Denmark

institute: Rigshospitalet

summary: Histone modifications are a key epigenetic mechanism to activate or repress the expression of genes. Data sets of matched microarray expression data and histone modification data measured by ChIP-seq exist, but methods for integrative analysis of both data types are still rare. Here, we present a novel bioinformatic approach to detect genes that are differentially expressed between two conditions putatively caused by alterations in histone modification. We introduce a correlation measure for integrative analysis of ChIP-seq and gene expression data and demonstrate that a proper normalization of the ChIP-seq data is crucial. We suggest applying Bayesian mixture models of different distributions to further study the distribution of the correlation measure. The implicit classification of the mixture models is used to detect genes with differences between two conditions in both gene expression and histone modification. The method is applied to different data sets and its superiority to a naive separate analysis of both data types is demonstrated. This GEO series contains the expression data of the Cebpa example data set.

overall_design: This data set was derived from sorted Cebpafl/fl and Cebpafl/fl;Mx1Cre murine hematopoietic LSKCD150- 18 post pIpC injections (conditional deletion of Cebpa). The specimens from three Cebpafl/fl and three Cebpafl/fl;Mx1Cre mice were hybridized separately on six Affymetrix Mouse Gene 1.0 ST arrays. Associated histone modification ChIP-seq data is provided by series GSE43007.

first: Hans-Ulrich

last: Klein

first: Martin

last: Schäfer

first: Bo

last: Porse

first: Katja

last: Ickstadt

last: Dugas


title: Microarray analysis of gene expression profile in MPTP-treated mouse retina: Comparative analysis of short-and long-term gene regulation

status: Public on Feb 10 2014

city: Seoul

first: Sabina

last: Lim

address: #1 Hoegi-dong Dongdaemoon-gu

country: South Korea

institute: East-West Medical Research Institute, Kyung Hee University

summary: To characterize both short- and long-term (7 days and 28 days) gene expression profiling differences between control and MPTP-treated retina, we determined levels of gene expression using microarray analysis and real-time PCR. We found 60 genes relatively regulated in retinas treated with MPTP for 7 days (26 up-regulated and 34 down-regulated), whereas 54 genes were regulated in retinas treated with MPTP for 28 days (18 up-regulated and 36 down-regulated) when compared with the non-treated retina in each control groups. Total 26 annotated differently expressed genes were chosen for further validation by quantitative real-time PCR, and 4 genes in the 7-day treatment group (Clec2e; Dio2; Hmcn1; Rlbp1) and 3 genes in the 28-days treatment group (Pnmt; Tmem121; Ssxb3) were confirmed.

overall_design: Male C57BL/6 mice  were randomly divided into four treatment groups (n= 6 in each group): the 7 days and 28 days saline-injection (control) groups (C-7 and C-28, respectively), and 7 days and 28 days MPTP-injection groups (M-7 and M-28, respectively). 4 retinas for 1 samples (1 gene chip),  (4 experimental group × 2 samples of each experimental group = total 8 samples).

first: Yeon-Mi

last: Hong

first: Yeong-Gon

last: Choi

first: Sujung

last: Yeo


title: Expression data from Sotos syndrome patients and controls

city: Leiden

first: Remco

last: Visser

address: Albinusdreef 2

department: Department of Pediatrics, J6-S

country: Netherlands

institute: Leiden University Medical Center

summary:
Genome-wide expression studies were performed on dermal fibroblasts from Sotos syndrome patients with a confirmed NSD1 abnormality and compared with age-sex matched controls.
We used microarrays to detect differentially expressed genes in Sotos syndrome patients and performed a global test with the aim to map NSD1 within a signaling transduction pathway.

overall_design: Dermal fibroblasts were obtained from nine Sotos syndrome patients and nine controls. Since NSD1 is a co-factor of the retinoic acid receptor, cultures were performed both in the presence and absence of retinoic acid.

first: R


title: Gene methylation profiles in visceral adipose tissue of obese men with and without the metabolic syndrome

status: Public on Feb 07 2014

city: Quebec

first: Frederic

last: Guenard

address: 2440, Hochelage blvd

country: Canada

institute: Laval University

type: Methylation profiling by genome tiling array

summary: Evaluate differences in gene methylation levels between obese men with and without the metabolic syndrome

overall_design: Visceral adipose tissue from obese men with the metabolic syndrome (MetS+, N=7) vs. obese men without the metabolic syndrome (MetS-, N=7)

first: Frédéric

last: Guénard

first: André

last: Tchernof

first: Yves

last: Deshaies

first: Louis

last: Pérusse

first: Simon

last: Biron

first: Odette

last: Lescelleur

first: Laurent

last: Biertho

last: Marceau

first: Marie-Claude

last: Vohl


title: Runx2-mediated gene regulation is affected by its genomic occupancy

status: Public on Feb 13 2014

city: Burlington

first: Jonathan

middle: AR

last: Gordon

state: VT

address: 89 Beaumont Ave Given E209

department: Biochemistry

institute: University of Vermont

summary: Osteogenesis is a highly regulated developmental process and continues during the turnover and repair of mature bone. Runx2, the master regulator of osteoblastogenesis, directs a transcription program essential for bone formation through both genetic and epigenetic mechanisms. While individual Runx2 gene targets have been identified, further insights into the broad spectrum of Runx2 functions required for osteogenesis are needed. By performing genome-wide characterization of Runx2 binding at the three major stages of osteoblast differentiation: proliferation, matrix deposition and mineralization, we identified Runx2-dependent regulatory networks driving bone formation. Using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) over the course of these stages, we discovered close to 80,000 significantly enriched regions of Runx2 binding throughout the mouse genome. These binding events exhibited distinct patterns during osteogenesis, and were associated with proximal promoters as well as a large percentage of Runx2 occupancy in non-promoter regions: upstream, introns, exons, transcription termination site (TTS) regions, and intergenic regions. These peaks were partitioned into clusters that are associated with genes in complex biological processes that support bone formation. Using Affymetrix expression profiling of differentiating osteoblasts depleted of Runx2, we identified novel Runx2 targets including Ezh2, a critical epigenetic regulator; Crabp2, a retinoic acid signaling component; Adamts4 and Tnfrsf19, two remodelers of extracellular matrix. We demonstrated by luciferase assays that these novel biological targets are regulated by Runx2 occupancy at non-promoter regions. Our data establish that Runx2 interactions with chromatin across the genome reveal novel genes, pathways and transcriptional mechanisms that contribute to the regulation of osteoblastogenesis.

overall_design: MC3T3-E1 cells were treated with scramble or Runx2 shRNA, then harvested at proliferating stage (day 0) and differentiating stage (day 9). Total RNAs recovered from these cells were hybridization on Affymetrix microarrays. We sought to find new target genes or pathways regulated by Runx2 during osteoblast differentiation. When combined with genome-wide occupancy of Runx2, we expect to gain new insights on how Runx2 controls a transcriptional program essential for osteoblast differentiation.

first: Hai

last: Wu

first: Troy

last: Whitfield

middle: A

first: Jason

last: Dobson

first: Phillip

last: Tai

first: Andre

middle: J

last: van Wijnen

first: Janet

middle: L

last: Stein

first: Gary

first: Jane

middle: B

last: Lian


title: Premature termination of in vivo reprogramming leads to cancer development through altered epigenetic regulation [array]

city: Tokyo

first: Yasuhiro

last: Yamada

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

department: Department of Molecular Pathology

country: Japan

institute: University of Tokyo

summary: We report a reprogrammable mouse system in which reprogramming factor expression in vivo can be controlled temporally by treatment with doxycycline (Dox).  Transient expression of reprogramming factors in vivo results in tumor development in various tissues, consisting of undifferentiated dysplastic cells.  We analyzed the kidney tumors developed in reprogrammable mice for global gene expressions and DNA methylations.

overall_design: Reprogrammable mice at 4 weeks of age were treated with Dox for 7 days followed by the withdrawal.  Seven days after the withdrawal, kidney tumors were analyzed for gene expressions and DNA methylations with microarray and RRBS method, respectively.  Normal kidney tissue at the same age and ES cells were analyzed as controls.  To examine the early changes of gene expressions, transgene-expressing kidney cells were FACS sorted and they are utilized for microarray analysis.  Primary liver tumors in reprogrammable mice and transplanted secondary kidney tumors in the subcutaneous tissues of immnodeficient mice were also analyzed for gene expressions.

first: Katsunori

last: Semi


title: Expression data from M0505 and STOSE murine ovarian surface epithelial cell lines

status: Public on Feb 04 2014

city: Ottawa

first: Barbara

middle: C.

last: Vanderhyden

state: ON

address: 501 Smyth Rd.

department: Cellular and Molecular Medicine

institute: University of Ottawa

summary:
Our lab established the M0505 cell line from the ovarian surface epithelium (OSE) of FVB/N mice in May 2005 in order to study OSE biology. This cell line spontaneously transformed into the spontaneously transformed OSE (STOSE) cell line in mid 2012.
We used microarrays to try to determine the molecular pathways that may have lead to the transformation of M0505 cells into STOSE cells to gain information that may lead to a greater understanding of human ovarian cancer initiation.

overall_design: Three biological replicates of M0505 and STOSE cell were collected for RNA extraction and subesequent hybridization on the Affymetrix GPL6246 platform.

first: Curtis

last: McCloskey


title: Altered Expression of Intraflagellar Transport Genes is Associated with Short Cilia in Smoking and COPD

status: Public on Feb 03 2014

city: New York

first: Yael

last: Strulovici-Barel

state: NY

address: 1300 York Avenue

department: Department of Genetic Medicine

institute: Weill Cornell Medical College

summary:
Study Smoking and COPD are associated with decreased mucociliary clearance and healthy smokers have shorter cilia in the large airway than nonsmokers. Intraflagellar transport (IFT) is the process by which cilia are produced and maintained. We assessed expression of IFT-related genes in smokers and nonsmokers and evaluated cilia length in the large and small airway of nonsmokers, healthy smokers, and smokers with COPD.
Methods Airway epithelium was obtained via bronchoscopic brushing. Affymetrix microarrays were used to evaluate IFT gene expression in 2 independent data sets from large and small airway. Cilia length was assessed by measuring 100 cilia (10 cilia on each of 10 cells) per subject.
Results All 40 IFT genes were expressed in the human large and small airway epithelium. In the large airway, 10 IFT genes were down-regulated and 1 up-regulated in smokers. In the small airway, 11 genes were down-regulated and 3 up-regulated in smokers. A set of 8 IFT genes was down-regulated in both data sets. In the large and small airway epithelium, cilia were significantly shorter in healthy smokers than nonsmokers, and significantly shorter in COPD smokers than in both healthy smokers and nonsmokers.
Answer to the Question These results support the concept that loss of cilia length contributes to defective mucociliary clearance in COPD, and that smoking-induced changes in expression of IFT genes may be one mechanism of abnormally short cilia in smokers. Strategies to normalize cilia length may be an important avenue for novel COPD therapies.

overall_design: Gene expression was assessed for 40 intraflagellar transport related genes in the LAE of nonsmokers (n=21) and healthy smokers (n=31) and the SAE of an independent group of nonsmokers (n=28) and healthy smokers (n=69).  Cilia length was assessed in a total of 228 airway epithelium samples, including 120 LAE samples and 108 SAE samples; a subset of the 228 samples is represented among the 149 samples in this Series.

first: Justina

last: Hessel

first: Jonna

last: Heldrich

first: Jennifer

last: Fuller

first: Michelle

last: Staudt

first: Sharon

last: Radisch

first: Charleen

last: Hollmann

first: Ben-Gary

last: Harvey

first: Robert

last: Kaner

first: Jacqueline

last: Salit

first: Jenny

last: Yee-Levin

first: Sriram

last: Sridhar

first: Sreekumar

last: Pillai

first: Holly

last: Hilton

first: Gerhard

last: Wolff

first: Hans

last: Bitter

first: Sudha

last: Visvanathan

first: Jay

last: Fine

first: Christopher

last: Stevenson

first: Ronald

middle: G

last: Crystal

first: Ann

middle: E

last: Tilley


title: Nuclear factor kappa B activation-induced anti-apoptosis renders HER2 positive cells drug resistant and accelerates tumor growth

city: Boston

first: Shannon

middle: Terrell

last: Bailey

state: MA

address: 450 Brookline Avenue, D728

department: Medical Oncology

institute: Dana-Farber Cancer Institute

summary:
Breast cancers with HER2 overexpression are sensitive to drugs targeting the receptor or its kinase activity. HER2-targeting drugs are initially effective against HER2- positive breast cancer, but resistance inevitably occurs. We previously found that nuclear factor kappa B is hyper-activated in the subset of HER-2 positive breast cancer cells and tissue specimens. In this study, we report that constitutively active NF-κB rendered HER2-positive cancer cells resistant to anti-HER2 drugs, and cells selected for Lapatinib resistance up-regulated NF-κB. In both circumstances, cells were anti-apoptotic and grew rapidly as xenografts. Lapatinib-resistant cells were refractory to HER2 and NF-κB inhibitors alone but were sensitive to their combination, suggesting a novel therapeutic strategy. A subset of NF-κB-responsive genes was overexpressed in HER2-positive and triple-negative breast cancers, and patients with this NF-κB signature had poor clinical outcome. Anti-HER2 drug resistance may be a consequence of NF-κB activation, and selection for resistance results in NF-κB activation, suggesting this transcription factor is central to oncogenesis and drug resistance. Clinically, the combined targeting of HER2 and NF-κB suggests a potential treatment paradigm for patients who relapse after anti-HER2 therapy. Patients with these cancers may be treated by simultaneously suppressing HER2 signaling and NF-κB activation.
We used microarrays to detail the gene expression differences underlying the characterictic survival differences between the SKR6, SKR6-Vector, SKR6CA, and SKR6LR cell lines, which are defined as follows: SKR6: A clonal derivative of SKBR3 cells isolated by fluorescence-activated cell sorting (FACS) to enrich for elevated HER2 levels, SKR6CA: SKR6 cells retrovirally transduced with constitutively active NF-κB relA/p65 (CAp65) and selected with puromycin, SKR6 vector: SKR6 cells transduced with the pQCXIP empty retroviral vector and selected with puromycin, and SKR6LR: SKR6 cells treated with increasing lapatinib concentrations (0.2 to 5 μM) for several months.

overall_design: We sorted SKBR-3 cells by fluorescence-activated cell sorting (FACS) to enriched for  cell population with elevated HER2 expression, which we termed SKR6. The following cell lines were then created from SKR6 cells: SKR6CA: SKR6 cells retrovirally transduced with constitutively active NF-κB relA/p65 (CAp65), SKR6 vector: SKR6 cells transduced with the pQCXIP empty retroviral vector and selected with puromycin, and SKR6LR: SKR6 cells treated with increasing lapatinib concentrations (0.2 to 5 μM) for several months.

middle: T

first: Penelope

last: Miron

first: Yoon

last: Choi

first: Bose

last: Kochupurakkal

first: Gautam

last: Maulik

first: Scott

last: Rodig

first: Ruiyang

last: Tian

first: Kathleen

last: Foley

first: Teresa

last: Bowman

first: Alexander

first: Myles

last: Brown

first: J

middle: D

last: Iglehart

first: Debajit

middle: K

last: Biswas


title: gamma-catenin (junction plakoglobin, Jup) dependent signals mediate the progression of BCR-ABL1+ B-ALL

status: Public on Feb 08 2014

city: Epalinges

first: Werner

last: Held

address: Chemin des Boveresses 155

department: Ludwig Center for Cancer Research

country: Switzerland

institute: University of Lausanne

summary:
The BCR-ABL1 translocation product is the cause of Chronic Myeloid Leukemia (CML) and of a significant fraction of adult-onset B-Acute Lymphoblastic Leukemia (B-ALL) cases. Here we identify an essential role for gamma-catenin (junction plakoglobin) in B lineage restricted cells for the progression of B-ALL in a mouse model. The array analysis of preleukemic B cells aimed at identifying genes that explain the deficient B-ALL progression in the absence gamma-catenin.
Total bone marrow cells from chimeric mice expressing or lacking gamma-catenin in the hematopoietic compartment were transduced with BCR-ABL1+ IRES GFP retrovirus before transplantation into lethally irradiated wild type recipients. Three weeks later, GFP+ (BCR-ABL1+) B220+ BP-1+ B cells were flow sorted from the bone marrow of preleukemic recipient mice.

overall_design: The analysis includes 3 replicates for gamma-catenin WT and 3 replicates for gamma-catenin KO BCR-ABL1+ BP1+ B cells.

first: Noémie

last: Gardiol


title: Transcription profiling by array of HC11 mammary epithelial cell strains stably expressing different variants of the transcriptional regulator megakaryoblastic leukemia-1 (Mkl1)

city: Basel

first: Tim

last: Roloff

address: Maulbeerstrasse 66

department: Functional Genomics

institute: FMI

summary: We have previously shown that HC11 mammary epithelial cells react strongly to the overexpression of megakaryoblastic leukemia-1 (Mkl1) with induction of tenascin-C expression. The present study was designed to find genes co-regulated with tenascin-C by Mkl1 in a SAP domain-dependent manner and without the involvement of serum response factor (SRF). For this purpose, we compared the transcriptomes of three stable HC11 cell strains that either overexpress full length Mkl1-RFP (HC11-FL), Mkl1-RFP with a mutated SRF-interaction site (HC11-mutB1) or Mkl1-RFP with a deletion of the SAP domain (HC11-ΔSAP).

overall_design: HC11 cell strains stably expressing either FL-, mutB1- or ∆SAP-Mkl1-RFP clones were grown in triplicates in 0.03% FCS/RPMI medium without EGF for 48 h before total RNA was extracted. RNA was converted into labeled cDNA and hybridized to Affymetrix GeneChip Mouse Gene 1.0 ST arrays. RMA normalized expression values were calculated with the affy package from the Bioconductor 2.4 release (1) and differentially expressed genes were identified using moderated t-statistics calculated with the empirical Bayes method as implemented in the Bioconductor limma package (2). To be considered as differentially expressed between HC11-mutB1 and HC11-FL as well as HC11-∆SAP and HC11-FL cell lines, genes had to pass the filters: adjusted P-value ≤ 0.01 (with Benjamin-Hochberg false discovery correction), a minimum absolute linear fold change difference of 2.0 and a minimum average expression value of 4.0 (log2).  References:  (1) Gentleman, R., Carey, V., Bates, D., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., Hornik, K., Hothorn, T., Huber, W., Iacus, S., Irizarry, R., Leisch, F., Li, C., Maechler, M., Rossini, A., Sawitzki, G., Smith, C., Smyth, G., Tierney, L., Yang, J., Zhang, J. (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biology 5, R80  (2) Smyth, G. K., Speed, T. (2003) Normalization of cDNA microarray data. Methods 31, 265-273

first: Maria

last: Asparuhova

first: Stephane

last: Thiry


title: Hemangioblast skewing from embryonic stem(ES) cells by defined factors

city: St. Louis

first: Fang

last: Liu

state: MO

address: 660S Euclid Ave.

department: Pathology & Immunology

institute: Washington University in St. Louis

summary: Successful derivation of a specific cell lineage from pluripotent stem cells will tremendously facilitate the clinical usage of pluripotent stem derived somatic cells. Herein, we demonstrate that ER71/Etv2, GATA2 and Scl form a core network in hemangioblast development and that transient co-expression of these three factors robustly induced hemangioblasts from ES cells. Such induced hemangioblasts potently generated hematopoietic and endothelial cells in culture as well as in vivo, warranting the evaluation of these cells in the future for repairing and/or regenerating hematopoietic and/or angiogenic defects.

overall_design: We have established a doxycycline inducible ES cell, iEGS, in which ER71/Etv2, GATA2 three transcription factors can be transiently co-expressed by doxycycline induction. We further analyzed the downstream target genes and signaling pathways at 6, 12 and 24hrs after ER71/Etv2, GATA2 induction. These data were obtained from three independent experiments.

first: Jinsheng

last: Yu

first: Kyunghee


title: Identification of TNFα-induced genes that are IRAK1BP1 dependent

city: Indianapolis

first: Maureen

last: Harrington

address: 635 Barnhill Dr

department: Biochemistry & Mol Bio

institute: Indiana University

summary: Tumor Necrosis Factor-alpha (TNFα) is a potent inducer of NF-κB dependent gene expression and IRAK1BP1 is required for TNFα-induced NF-κB activity.  Microarrays were used to identify the subset of TNFα-induced genes that are also IRAK1BP1 dependent.

overall_design: Wild type and KO plus and minus treatment


title: Quantitative reconstruction of leukocyte subsets using DNA methylation

first: William

middle: P

last: Accomando

address: Kresge Bldg 911, 677 Huntington Ave

department: Epidemiology

institute: Harvard School of Public Health

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

overall_design: Refer to individual Series


title: Array-based assay detects genome-wide 5-methylcytosine and 5-hydroxymethlycytosine in non-human primates and mice

city: Atlanta

first: Pankaj

last: Chopra

state: GA

address: 615 Michael St. NE, Ste. 375

department: Human Genetics

institute: Emory University

summary: Murine and non-human primates (e.g. rhesus monkeys) represent excellent model systems to study human health and disease. However, use of these model systems for genomic studies is limited, particularly with array-based tools, as most have only been developed to survey the human genome. Here we present the optimization of a widely used human DNA methylation array, designed to detect 5-methylcytosine (5-mC), and show that non-human data generated using the optimized array reproducibly distinguishes tissue types within and between chimpanzee, rhesus, and mouse, with correlations near the human DNA level (R2 > 0.99). Genome-wide methylation analysis, using this approach, reveals 6,102 differentially methylated loci between rhesus placental and fetal tissues with pathways analysis significantly overrepresented for developmental processes. Restricting the analysis to oncogenes and tumor suppressors genes finds 125 differentially methylated loci, suggesting that rhesus placental tissue carries a cancer epigenetic signature. Moreover, we adapted the assay to detect 5-hydroxymethylcytosine (5-hmC) and find highly reproducible 5-hmC levels within human, rhesus, and mouse brain tissue that is species-specific with a hierarchical abundance among the three species (human > rhesus >> mouse). Together, these data show that this array-based methylation assay is generalizable to all mammals for the detection of both 5-mC and 5-hmC, greatly improving the utility of mammalian model systems to study the role of epigenetics in human health, disease, and evolution.

sample_organism:
Macaca mulatta
Pan troglodytes
Homo sapiens
Mus musculus

first: Reid

last: Alisch


title: Tumoral transcriptome profiling of tPTEN-/- mice.

city: Valbonne - Sophia-Antipolis

first: Kevin

last: Lebrigand

address: 660 route des lucioles

country: France

institute: IPMC/CNRS

summary: tPTEN-/- mice display a deletion of the PTEN tumor suppressor gene specifically in T cells (cross PTEN flox/flox x lck-Cre). They develop T cell lymphoma with a primary thymic tumor and invasion of most organ at late stage of the disease.

overall_design: Gene profiling was performed on whole tumors (ST3 stage 3 invasive lymphoma) and normal thymocytes (wt) using Affymetrix-MoGene-1_0-st-v1 chips.

middle: F

last: Peyron

first: B

last: Mari

first: K

first: P

last: Barbry

first: C

last: Moreilhon

first: V

last: Imbert-rezzonico


title: Gene expression profiling reveals biological pathways responsible for phenotypic heterogeneity between UK and Sri Lankan OSCC

status: Public on Feb 02 2014

city: edinburgh

first: anas

middle: amjad

last: saeed

address: Lauriston building

department: oral surgery

country: United Kingdom

institute: edinburgh dental institute

summary:
Background: Oral squamous cell carcinoma (OSCC) is a major world health problem with over 400,000 new cases diagnosed annually.  Despite advances in surgery and chemo-radiotherapy, the 5 year survival has remained roughly constant at approximately 50% for several decades.  The disease is characterized by both clinical and genetic heterogeneity, so elucidating the molecular basis of this heterogeneity would have significant clinical implications.  It is well recognized that OSCCs from Asia that are associated with betel quid chewing are phenotypically distinct from those from the West that are predominantly caused by smoking/drinking, but the genetic basis of these differences are largely unknown. The aim of this study is to examine the most related genetic factors, carcinogenic related pathways, and molecular processes that might be responsible for the phenotypic heterogeneity of OSCC between UK and Sri Lankan population groups.   Methods: We have compared the gene expression profiles of OSCCs and normal oral mucosal tissues from both Sri Lankan and UK individuals using Affymetrix gene expression arrays.
Results: The gene expression profiles of UK and Sri Lankan OSCC are similar in many respects to other oral cancer expression profiles reported in the literature and were mainly similar to each other.  However, genes involved in tumor invasion, metastasis and recurrence were more obviously associated with UK tumors as opposed to those from Sri Lanka.  Interestingly, Ingenuity Pathway Analysis (IPA) revealed a highly activated cell-mediated immune response in both Sri Lankan normal and tumor samples relative to UK cohorts, which may, in part, explain the less aggressive behavior of these betel quid-induced OSCCs.  Conclusion: The development of OSCCs in both UK and Sri Lankan populations appears largely mediated by similar biological pathways despite the differences related to race, ethnicity, lifestyle, and/or exposure to environmental carcinogens. However, IPA revealed a highly activated “Cell-mediated Immune Response” in Sri Lankan normal and tumor samples relative to UK cohorts. It seems likely, therefore, that any future attempts to personalize treatment for OSCC patients will need to be different in Western and Asian countries to reflect differences in gene expression and the immune status of the patients.

overall_design: All biopsy specimens of OSCC and normal oral mucosa were harvested with appropriate ethical approval and informed consent of individual patients (LREC 0769). Identical protocols for tissue collection and processing were used in both countries. OSCC samples were obtained from sequential incident cases treated by a single consultant surgeon from 2001 to 2004 at University Hospital of Birmingham, NHS Foundation Trust, Birmingham, UK, and Kandy General Hospital, Kandy, Sri Lanka. A total of 21 UK and 27 Sri Lankan samples yielded RNA of sufficient quality and quantity for microarray analysis. In addition, 8 normal oral mucosa specimens (five samples from UK & three samples from Sri Lankan population) were also profiled. All normal samples were from non-smokers, who did not chew betel quid and did not consume in excess of the national recommended weekly gender allowance of alcohol. Normal samples were taken from individuals with no history of cancer and had no first degree relatives with a history of cancer.

first: Anas

last: Saeed

first: Andrew

middle: H

last: Sims

first: Stephen

last: Prime

first: Ian

last: Paterson

first: Paul

last: Murray

first: Victor

middle: R

last: Lopes


title: Affymetric 1.0 ST exon array comparing gene expression of bone marrow derived macrophage lacking beta-catenin with control macrophages

status: Public on Feb 01 2014

city: Toronto

first: Saeid

last: Amini-Nik

address: 101 College St

institute: Hospital For Sick Children

summary: Bone marrow derived macrophages of Lysz-Cre;Catnbtm2Kem(fl/fl) mouse were compared with bone marrow derived macrophage of Catnbtm2Kem(fl/fl) control mouse

overall_design: Total RNA extracted from bone marrow derived macrophage

first: Benjamin

last: Alman


title: Small intestine intraepithelial CD4+ T cells after Toxoplasma gondii infection

status: Public on Feb 15 2014

first: Marco

last: Colonna

address: 660 S Euclid Ave.

department: Pathology and Immunology

institute: Washington University School of Medicine

summary: Retention of lymphocytes in the intestinal mucosa requires specialized chemokine receptors and adhesion molecules. Here we find that both CD4+CD8+ and CD4+T cells in the intestinal epithelium, as well as CD8+T cells in the intestinal mucosa and mesenteric lymph nodes, express the cell adhesion molecule Crtam upon activation, whereas the ligand of Crtam, Cadm1, is expressed on gut CD103+DCs. Lack of Crtam-Cadm1 interactions in Crtam-/- and Cadm1-/- mice results in loss of CD4+CD8+T cells, which arise from mucosal CD4+T cells that acquire a CD8 lineage expression profile. Following acute oral infection with T. gondii, both WT and Crtam-/- mice mounted a robust TH1 response, but markedly fewer TH17 cells were present in the intestinal mucosa of Crtam-/- mice. The almost exclusive TH1 response in Crtam-/- mice resulted in more efficient control of intestinal T. gondii infection.

overall_design: CD4+ T cells were cell sorted to analyze the differences resulting from the lack of Crtam expression during T. gondii infection.

middle: S

last: Cortez

first: Luisa

last: Cervantes-Barragan


title: Transcriptomic analysis of prometastatic and metastasis-resistant lungs from mice

first: Dingcheng

last: Gao

address: 1300 York Ave

department: CT Surgery

summary: We describe the gene expression profile of metastasis-prone lungs of mice after injection of LN4-tumor cell conditioned media intraperitoneally for one week, compared to the metastasis-inhibitory PC3 tumor cell conditioned media, which is the parental cell line to LN4

overall_design: 2 mice injected with RPMI medium (control), 2 mice injected with PC3-derived conditioned medium, and 2 mice injected with PC3M-LN4 conditioned medium

first: Raul

last: Catena

first: Vivek

last: Mitta


title: Transcriptomic analysis of mammary tumors from MMTV-ErbB2 transgenic mice

city: Berkeley

first: Jian-Hua

last: Mao

address: One Cyclotron Road

institute: Lawrence Berkeley National Laboratory

summary: The tyrosine kinase ErbB2 positive breast tumors have more aggressive tumor growth, poorer clinical outcome, and more resistance to radiotherapy, chemotherapy and hormone therapy. A humanized anti-ErbB2 monoclonal antibody Herceptin and a small molecules inhibitor Lapatinib were developed and approved by FDA to treat patients with ErbB2 amplification and overexpression. Unfortunately, most ErbB2+ breast cancers do not respond to Herceptin and Lapatinib, and the majority of responders become resistant within 12 months of initial therapy (defined as secondary drug resistance). Such differences in response to Lapatinib treatment is contributed by substantial heterogeneity within ErbB2+ breast cancers. To address this possibility, we carried out transcriptomic analysis of mammary tumors from genetically diverse MMTV-ErbB2 mice. This will help us to have a better understanding of the heterogeneous response to ErbB2 targeted therapy and permit us to design better and more individualized (personalized) treatment strategies for human ErbB2 positive breast cancer.

overall_design: 214 MMTV-ErbB2 mammary tumors and 8 normal mammary glands were analyzed by Affymetrix microarrays.

first: Jesus

last: Perez-Losada


title: Transcriptional dissection of pancreatic tumors engrafted in mice

status: Public on Apr 22 2014

city: Madrid

first: Manuel

last: Hidalgo

state: Madrid

address: C/Melchor Fernandez Almagro 3

department: Clinical Research Programme

country: Spain

institute: CNIO

type:
Expression profiling by array
Third-party reanalysis

summary: Engraftment of primary pancreas ductal adenocarcinomas (PDAC) in mice to generate patient derived xenograft (PDX) models is a promising platform to for biological and therapeutic studies in this disease. However, these models are still incompletely characterized. Here, we measured the impact of the murine environment on the gene expression of the engrafted human tumoral cells. We have analyzed gene expression profiles from 35 new PDX models and compared them with previously published microarray data from PDAC and hepatocellular carcinoma (HCC). Our results showed that PDX models derived from PDAC, or HCC, were clearly different to the cell lines derived from the same cancer tissues. Indeed, PDAC- and HCC-derived cell lines are indistinguishable one from the other based in their gene expression profiles. In contrast, the transcriptomes of PDAC and HCC PDX models are clearly different and more similar to their original tumor than to PDX models from the other tumor type. Interestingly, the main differences between pancreatic PDX models and human PDAC is the expression of genes involved in pathways related with extracellular matrix interactions and cell cycle regulation likely reflecting the adaptations of the tumors to the new environment. Furthermore, most of these differences are detected in the first passages after the tumor engraftment, indicating early phases of the adaptation process. In conclusion, different from conventional cancer cell lines, PDX models of PDAC retain similar gene expression profiles of PDAC. Expression changes are mainly related to genes involved in stromal pathways likely reflecting the adaptation to new environments. We also provide evidence of the stability of gene expression patterns over subsequent passages.

overall_design: We have analyzed gene expression profiles from 35 new PDX models and compared them with previously published in GEO microarray data. We used PDX models, primary tumors and cell lines from PDAC and hepatocellular carcinoma. All these public data were re-process in order to compare with our 35 samples

first: Raquel

last: Martínez-García

first: Alfonso

last: Valencia


title: Effects of exercise on gene expression level in human monocytes

city: Irvine

first: Shlomit

last: Radom-Aizik

address: 101 Academy

department: Pediatrics

institute: University of California, Irvine

summary:
We tested the hypothesis on the mechanisms responsible for the early control of monocytes function by identifying a discrete set of genes in circulating monocytes that were altered by exercise.
Exercise leads to a rapid change in the profile of gene expression in monocytes.

overall_design: Twelve healthy men (22-30 yr old) performed 10 2-min bouts of cycle ergometer exercise interspersed with 1-min rest at a constant work equivalent to about 82% of VO2max. A baseline blood sample was taken before the and immediately after the exercise.  Monocytes  were isolated from PBMC using a negative magnetic cell separation methods (Miltenyi Biotec Monocyte Isolation Kit II human  #130-091-153 and the autoMACS® Pro Separator). Total RNA was extracted using TRIzol®.  For this study we used Affymetrix plus 2  (total of 24 chips).

first: Dan

middle: M

last: Cooper


title: Reprogramming of the Human Intestinal Epigenome by Surgical Tissue Transposition

city: Los Angeles

first: Fides

last: Lay

address: 615 Charles E Young Drive South, BSRB 457

department: MCDB

institute: UCLA

summary: Genome-wide DNA methylation profiling of human ileal neobladder samples.

overall_design: Bisulphite converted DNA from the 48 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

first: F

first: T

middle: J

last: Triche

first: P

middle: A

last: Jones

first: Y

last: Chihara


title: Effects of exercise on gene and miRNA expression level in human monocytes

type:
Expression profiling by array
Non-coding RNA profiling by array


title: Effect of genetic Zfx deletion on Myc induced gene expression in bone marrrow myeloid progenitors

status: Public on Jan 30 2014

first: Stuart

last: Weisberg

address: 650 W 168th Street

department: Pathology and Cell Biology

institute: Columbia University

summary: Acute myeloid leukemia (AML) and acute T-lymphoblastic leukemia (T-ALL) maintain the undifferentiated phenotype and proliferative capacity of their respective cells of origin, hematopoietic stem/progenitor cells and immature thymocytes. The mechanisms that maintain these progenitor-like characteristics are poorly understood. We report that the transcription factor Zfx is required for the development and propagation of experimental AML caused by MLL-AF9 fusion, and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx activated progenitor-associated gene expression programs and prevented differentiation. Key Zfx target genes included mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescued the propagation of Zfx-deficient AML. These studies identify a common mechanism that controls the cell-of-origin characteristics of acute leukemias derived from disparate lineages and transformation mechanisms.

overall_design: Bone marrow progenitors (c-Kit +) from Zfx wt/y CreER mice and Zfx fl/y CreER mice were harvested after tamoxifen administration to induce Cre. The Zfx wt and Zfx ko progenitors were infected with Myc expressing and control retrovirus with GFP selectable marker and cultured for 48 hours in cytokine supplemented media. The GFP + myeloid progenitors were sorted and cultured for another 4 days prior to RNA extraction.

first: Boris

middle: V

last: Reizis


title: Illumina Infinium HumanMethylation450 data for human whole blood samples and for mixtures of purified white blood cells reconstructing human blood

first: William

last: Accomando

summary: The objective of the study was to utilize DNA methylation to quantify human leukocyte subsets in human blood. This file contains data from an Illumina  Infinium HumanMethlation450  for human whole blood samples as well as complex mixtures of DNA from purified human leukocyte subtypes in quantities that mimick human blood under different clinical conditions.

overall_design: Bisulfite converted DNA from the  samples were hybridized to an Illumina Infinium HumanMethylation450 beadchip

first: John

last: Wiencke

first: Karl

last: Kelsey


title: Effect of genetic Zfx deletion on gene expression in Notch induced T-ALL

overall_design: Independent primary Notch induced T-ALL cell lines were created by retroviral transduction of Notch-IC into hematopoietic progenitors carrying the tamoxifen inducible Cre-ER transgene and the Zfx conditional (Zfx fl/y) allele (lines 14843, 14844, 14846).  T-ALL cells generated from each line were isolated from moribund mice and transplanted into sublethally irradiated secondary recipients. Ten days after transplant when T-ALL cells had appeared in the blood of the secondary recipients, they were treated by gavage with either Vehicle or Tamoxifen (5 mg /day for three days) to induce Zfx deletion in leukemia cells.  48 hours after the final Tamoxifen treatment, the mice were sacrificed and T-ALL cells were recovered by FACS for microarray studies.


title: BayMeth: improved DNA methylation quantification for affinity capture sequencing data using a flexible Bayesian approach

status: Public on Jan 25 2014

city: Zurich

first: Mark

last: Robinson

state: ZH

address: Winterthurerstrasse 190

institute: University of Zurich

summary: Affinity capture of DNA methylation combined with high-throughput sequencing strikes a good balance between the high cost of whole genome bisulfite sequencing and the low coverage of methylation arrays. We present BayMeth, an empirical Bayes approach that uses a fully methylated control sample to transform observed read counts into regional methylation levels. In our model, inefficient capture can readily be distinguished from low methylation levels. BayMeth improves on existing methods, allows explicit modeling of copy number variation, and offers computationally-efficient analytical mean and variance estimators. BayMeth is available in the Repitools Bioconductor package.

overall_design: Benchmarking samples to compare MBD- and MeDIP-seq [GSE38679, GSE24546; PMID 21045081] datasets against 450k measurements


title: Identification of protein kinase C beta 2 regulated genes early in dendritic cell differentiation

status: Public on Jan 29 2014

first: Gregory

middle: B

last: Lesinski

address: 1365C Clifton Rd. NE

department: Hematology and Medical Oncology

institute: Winship Cancer Institute of Emory University

summary: Dendritic cells (DC) arise from a diverse group of hematopoietic progenitors and have marked phenotypic and functional heterogeneity. We have found previously that activation of protein kinase C beta 2 (PRKCB2) by cytokines or phorbol esters drives normal human CD34(+) hematopoietic progenitors and myeloid leukemic blasts (KG1, K562 cell lines, and primary patient blasts) to differentiate into DC, but the genetic program triggered by PRKCB2 activation that results in DC differentiation is only beginning to be characterized. Of the cPKC isoforms, only PRKCB2 was consistently activated by DC differentiation-inducing stimuli in normal and leukemic progenitors. To examine early changes in gene expression following PRKCB2 activation, we employed the following cell lines: (1) the CD34(+) human acute myeloid leukemia derived cell line KG1, which undergoes DC differentiation following phorbol ester treatment; (2) KG1a, a spontaneously arising differentiation-resistant daughter cell line of KG1 that has lost PRKCB2 expression; (3) clones established from KG1a that stably express exogenous PRKCB2-GFP fusion proteins and are once again able to undergo DC differentiation (KG1a-PRKCB2-GFP Clone E9 and Clone E11). We examined changes in gene expression in these cells following treatment with the phorbol ester PMA (phorbol 12-myristate 13-acetate) for 2 hours. Since KG1 and KG1a differ in PRKCB2 expression but have similar expression of the other protein kinase C isoforms, this protocol will allow for the identification of genes regulated by PRKCB2 activation.

overall_design: KG1, KG1a, E9, and E11 were cultured for 2 hours in normal media +/- PMA (10 ng/ml). RNA was then isolated using RNeasy mini-columns (Qiagen) following the standard protocol. Samples were then sent to Expression Analysis, who carried out quality control, sample processing/labeling, hybridization to Affymetrix GeneChip arrays (Human U133 2.0 Plus), imaging, and analysis according to their standard protocols. Gene expression profiles were generated for each cell line in the presence and absence of phorbol ester stimulation, for a total of 12 samples (E9 +/- PMA and E11 +/- PMA were run in duplicate).

first: Pedro

last: Cejas

first: Louise

last: Carlson

first: Matthew

last: Farren

first: Kelvin

last: Lee


title: Methylation profiling classifies HIV-associated lymphoma

city: Shinjuku

first: Akihiro

last: Matsunaga

state: Tokyo

department: Intractable Disease

institute: National Center for Global Health and Medicine

summary: HIV-positive patients have a higher risk of non-Hodgkin's lymphoma with poor prognostic features. To characterize features of HIV-associated lymphoma, we compared the genome-wide DNA methylation profiles in between 11 HIV-associated and 20 non-HIV lymphoma samples by Illumina Infinium HumanMethylation450 BeadChip v1.0.

overall_design: Bisulfite-converted DNA from the 31 samples were analyzed to obtain the genome-wide methylation profile by using Illumina Infinium HumanMethylation450 BeadChip microarray.

first: Tsunekazu

last: Hishima

first: Noriko

last: Tanaka

first: Maria

last: Yamazaki

first: Makoto

last: Motizuki

first: Yukihito

last: Ishizaka

first: Mari

last: Shimura

first: Shotaro

last: Hagiwara


title: Effect of genetic Zfx deletion on gene expression in c-Kit + MLL-AF9 AML cells

first: Stuart

last: Weisberg

summary:
Acute myeloid leukemia (AML) propagates as a cellular hierarchy which is maintained by a rare subpopulation of self-renewing leukemia-initiating cells (LICs). These LICs phenotypically resemble HSCs and early myeloid progenitors, and they are functionally defined by their ability to reconstitute AML in xenografted mice.
Common transcriptional regulators are believed to drive self-renewal of LICs and normal stem cells. Examples include the histone methyltransferase, MLL and its main targets, the transcription factors HOXA9 and MEIS1; the polycomb group protein, BMI-1; and the Wnt/β-catenin signaling pathway4-9. In AML patients, LICs have been shown to share broad gene expression signatures with hematopoietic stem cells (HSCs) and, in some cases, with embryonic stem cells (ESCs). Moreover, increased expression of these stem cell signatures has been linked to tumor aggressiveness.
Elucidating the molecular determinants of stem cell properties in LICs has the potential to improve AML therapy and clarify the relationship between cancer and stem cell biology in general. Here we show that the propagation of LICs in AML depends on Zfx, a transcription factor required for the self-renewal of ESCs and HSCs. Using mouse models, we found that Zfx is required for AML propagation and LIC maintenance. We defined a Zfx-driven gene expression program in murine LICs that correlates with existing stem cell-related gene expression signatures in AML patients. Using a novel, stroma-based RNAi screening strategy, we identified functionally important Zfx target genes. Two of these genes – FAM92A1 and DOCK7 - are required for human AML cell propagation; moreover, their expression levels strongly correlate with AML patient survival across the full spectrum of AML subtypes. Together, our results characterize a novel gene expression program that orchestrates critical stem cell properties of LICs, and drives aggressiveness of AML.

overall_design: Independent primary MLL-AF9 AML cell lines were created carrying the tamoxifen inducible Cre-ER transgene and either the Zfx wild-type (wt/y) (lines 10977, 10980) or the Zfx conditional (Zfx fl/y) allele (lines 10949, 10950, 10986). AML cells generated from each line were isolated from moribund mice and cultured with or without 4-hydroxytamoxifen for 72 hours to induce Cre. After Cre induction, c-Kit + cells were purified by FACS and processed for microarray studies.

first: Boris

last: Reizis


title: HDAC and aminopeptidase inhibitor treatment of myeloma cells

status: Public on Jan 24 2014

city: Sutton

first: Emma

middle: Marie

last: Smith

address: 15 Cotswold Road

department: Haemato-Oncology

institute: Institute of Cancer Research

summary:
H929 human myeloma cells were exposed to aminopeptidase inhibitor (CHR-2797), HDAC inhibitor (CHR-3996), or a combinaion of the two agents, for 24 hours.
Following this treatment RNA was extracted and microarrays used to determine gene expression changes.

overall_design: Myeloma cells were exposed to chemotherapeutic agent for 24 hours.

first: E

first: F

last: Davies


title: Expression data from L-02 and Hep3B cells

status: Public on Jan 23 2014

city: Guangzhou

first: Yuan

last: Lin

state: Guangdong

address: No.74, Zhongshan 2nd Rd.

country: China

institute: Sun Yat-sen University

summary:
Constitutively expressed intracellular antiviral factors are responsible for the resistance of cells against alphavirus, especially for the inhibition of virus entry and early replication.
We used microarrays to compare the gene expression profiles between resistant (L-02) and susceptible (Hep3B) cells and identified the antiviral genes that are defective in susceptible cells.

overall_design: RNA were extracted from normally cultured L-02 and Hep3B cells. cDNA and cRNA were produced and hybridized to Affymetrix microarrays.

first: Haipeng

last: Zhang


title: Loss of Lkb1 and Pten Leads to Lung Squamous Cell Carcinoma with Elevated Pdl1 Expression: Stroma Cells

city: Boston

first: Chunxiao

last: Xu

address: 450 Brookline Ave

department: Medical Oncology

institute: Dana Farber Cancer Institute

summary:
Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that bi-allelic inactivation of Lkb1 and Pten in the mouse lung led to SCC that recapitulated the histology, gene expression and microenvironment found in human disease. Lkb1/Pten-null (LP) tumors expressed the squamous markers Krt5, p63 and Sox2, and transcriptionally resembled the basal subtype of human SCC. In contrast to mouse adenocarcinomas, the LP tumors contained immune populations enriched for tumor-associated neutrophils. Sca1+/Ngfr+ fractions were enriched for tumor propagating cells (TPCs) that could serially transplant the disease in orthotopic assays. TPCs in the LP model and Ngfr+ cells in human SCCs highly expressed Pdl1, suggesting a novel mechanism of immune escape for TPCs.
We used microarrays to detail the gene expression profles among lung SCC tumor epitheial cell, lung ADC tumor epithelia cell and normal epithelial cells.

overall_design: Kras tumor stroma cells and LP tumor stroma cells were sorted by FACS, the cells were gated as EpCAM-/CD45+/CD31+

first: Christine

last: Fillmore


title: Loss of Lkb1 and Pten Leads to Lung Squamous Cell Carcinoma with Elevated Pdl1 Expression

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

overall_design: Refer to individual Series


title: Gene expression profiling of liver biopsies from 21 chronic hepatitis C patients undergoing antiviral therapy

first: Zuzanna

last: Makowska

address: Hebelstrasse 20

department: Biomedicine

institute: University of Basel

summary: Pegylated interferon-α (pegIFN-α) has replaced un-modified recombinant IFN-α for the treatment of chronic viral hepatitis because of its superior anti-viral efficacy that is generally attributed to improved pharmacokinetic properties. However, the pharmacodynamic effects of pegIFN-α in the liver have not been studied. We analyzed pegIFN-α induced signaling and gene regulation in paired liver biopsies obtained before treatment and during the first week after injection of pegIFN-α in 18 patients. Despite sustained high serum concentrations of pegIFN-α over the entire one-week dosing interval, IFN-α signaling through the Jak-STAT pathway occurs only during the first day. PegIFN-α induces hundreds of genes that can be classified into 4 clusters based on different temporal expression profiles. In all clusters, gene transcription is mainly driven by IFN stimulated gene factor 3 (ISGF3). IFN induced secondary transcription factors do not cause additional waves of gene expression. We could not confirm a role of un-phosphorylated STAT1 in prolonging IFN-α induced gene transcription. Collectively, our results reveal that the major effects of pegIFN-α in the liver are caused by an early and transient activation of ISGF3. Prolonging the serum half-life of IFN-α does not necessarily improve its pharmacodynamic properties.

overall_design: Paired liver biopsy samples were collected before and during the first week of pegylated interferon alpha treatment of 21 chronic hepatitis C patients.  Total: 21 patients and 42 samples.

first: Michael

last: Dill

first: Gaia

last: Trincucci

first: Andreas

last: Gruber

first: Julia

middle: E

last: Vogt

first: Magdalena

last: Filipowicz

first: Ilona

last: Krol

first: Luigi

last: Terracciano

first: Erik

last: van Nimwegen

first: Volker

last: Roth

first: Markus

last: Heim


title: Runx3 function in splenic NK cells activated in vivo by IL-15.

status: Public on Jan 22 2014

city: Rehovot

first: Joseph

last: Lotem

department: Molecular genetics

country: Israel

institute: Weizmann institute of science

summary: NK cells are innate immune cells that recognize and kill foreign, virally-infected and tumor cells without the need for prior immunization. NK expansion following viral infection is IL-2 or IL-15-dependent.

overall_design: To identify Runx3 regulated genes, NK cells were isolated from spleen of  IL15/Ra injected WT and Runx3-/- mice and sorted to obtain 3 subpopulations of immature (CD27) and mature (DP and CD11c) NK cells.

first: Ditsa

last: Levanon

first: Dena

last: Leshkowitz

first: Yoram

last: Groner


title: Genome-Scale Profiling of DNA Methylation in Sporadic Pituitary Macroadenomas: Association with Tumor Invasion and Histopathological Subtype

status: Public on Jan 28 2014

first: Chao

last: Ling

state: California

address: 1501 San Pablo street

department: Zilkha Neurogenetic Institute

institute: University of Southern California

summary: The pathophysiologic mechanisms driving tumorigenesis and invasion of sporadic pituitary macroadenomas (PAs) remain unknown. We hypothesized that alterations in DNA methylation are associated with PA invasion and histopathology subtype, and that genome-scale methylation analysis may complement current classification methods for sporadic PAs.

overall_design: Twenty-four surgically-resected sporadic PAs with varying histopathological subtypes were assigned dichotomized Knosp invasion scores and examined using genome-wide DNA methylation patterns and RNA sequencing.

first: Matthew

last: Pease

first: Lingling

last: Shi

first: Vasu

last: Punj

first: Mark

last: Shiroishi

first: Deborah

last: Commins

first: Daniel

last: Weisenberger

first: Kai

last: Wang

first: Gabriel

last: Zada


title: Gene expression analysis for Il13Ra2-positive and IL13Ra2-negative glioma cell lines

city: Duarte

first: Charles

middle: David

last: Warden

address: 1500 East Duarte Rd

department: Department of Molecular and Cellular Biology

institute: City of Hope

summary: Affymetrix expression profiling was used to evaluate the association between IL13Rα2 expression, and mesenchymal, proneural, classical and neural signature genes expression for glioma subclasses defined by Verhaak et al (Cancer Cell; 2010).

overall_design: The goal of this study is to compare gene expression patterns between IL13Ra2-postive and IL13Ra2-negative glioma cell lines. IL13Ra2 status was determined by flow cytometry and confirmed by qPCR.

first: Christine

last: Brown


title: Secretory Antibodies in Breast Milk Promote Long-Term Intestinal Homeostasis by Regulating the Gut Microbiota and Host Gene Expression.

city: Lexington

first: Charlotte

last: Kaetzel

state: KY

address: 800 Rose St.

department: Microbiology, Immunology & Molecular Genetics

institute: University of Kentucky

summary:
Maintenance of intestinal homeostasis requires a healthy relationship between the commensal gut microbiota and the host immune system. Breast milk supplies the first source of antigen-specific immune protection in the gastrointestinal tract of suckling mammals, in the form of secretory immunoglobulin A (SIgA). SIgA is transported across glandular and mucosal epithelial cells into external secretions by the polymeric immunoglobulin receptor (pIgR). Here, a breeding scheme with pIgR-sufficient and -deficient mice was used to study the effects of breast milk-derived SIgA on development of the gut microbiota and host intestinal immunity. Early exposure to maternal SIgA prevented the translocation of aerobic bacteria from the neonatal gut into draining lymph nodes, including the opportunistic pathogen Ochrobactrum anthropi. By the age of weaning, mice that received maternal SIgA in breast milk had a significantly different gut microbiota from mice that did not receive SIgA, and these differences were magnified when the mice reached adulthood. Early exposure to SIgA in breast milk resulted in a pattern of intestinal epithelial cell gene expression in adult mice that differed from that of mice that were not exposed to passive SIgA, including genes associated with intestinal inflammatory diseases in humans. Maternal SIgA was also found to ameliorate colonic damage caused by the epithelial-disrupting agent dextran sulfate sodium. These findings reveal unique mechanisms through which SIgA in breast milk may promote lifelong intestinal homeostasis, and provide additional evidence for the benefits of breastfeeding.
We used microarrays to determine the effects of passive and active secretory IgA, in the presence or absence of the epithelial-disrupting agent dextran sulfate sodium, on gene expression in intestinal epithelial cells of mice

overall_design: A breeding scheme was used that involved crosses between mouse dams and sires that were deficient or sufficient for expression of the polymeric immunoglobulin receptor (Pigr), a protein that is required for transport of secretory IgA (SIgA) into external secretions. Offspring of these crosses were genotyped for Pigr alleles, and littermate offspring were distributed into 4 groups based on early exposure to passive SIgA in mother's milk (P-yes and P-no) and ability to carry out Pigr-mediated endogenous transport of active SIgA (A-yes and A-no). Seventy-day-old gender-matched Pigr+/- and Pigr-/- offspring of Pigr+/- and Pigr-/-  dams were left untreated or given 2% dextran sulfate sodium (DSS) in drinking water for 8 days. Colonic epithelial cells were isolated, and total cellular RNA was purified. RNA was pooled from 3 mice for each of 2 biological replicates for microarray analysis.

first: Eric

middle: W

last: Rogier

first: Aubrey

middle: L

last: Frantz

first: Maria

last: Bruno

first: Leia

last: Wedlund

first: Donald

last: Cohen

first: Arnold

last: Stromberg


title: Key differences identified between actinic keratosis and cutaneous squamous cell carcinoma by transcriptome profiling

status: Public on Jan 21 2014

city: London

first: Sally

last: Lambert

address: Blizard Institute, 4 Newark Street

department: Centre for Cutaneous Research

institute: Queen Mary, University of London

summary:
Cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies in fair skinned populations worldwide and its incidence is increasing. Despite previous observations of multiple genetic abnormalities in cSCC, the oncogenic process remains elusive. The purpose of this study was to investigate the transcriptomes of cSCC and actinic keratoses (AK), to elucidate key differences between precursor AK lesions and invasive carcinoma.
This study identified 196 genes that are differentially expressed between AK and cSCC, with enrichment for processes including epidermal differentiation, cell migration, cell cycle regulation and metabolism. Gene set enrichment analysis highlighted a key role for the MAPK pathway in the transition from AK to cSCC. Furthermore, the differentiation status of the tumor influenced the gene expression profile, which may have implications for drug sensitivity and response in clinical trials. These data indicate that progression to cSCC is associated with a complex pattern of molecular changes. We have identified relevant pathways involved in this process, in particular that the MAPK pathway may be pivotal to the transition from AK and may represent a potential therapeutic target.

overall_design: RNA was extracted by laser capture microdissection from 10 AK and 30 cSCC, for analysis using the Affymetrix HG U133 Plus 2.0 microarrays. The cSCC samples included a range of histological diagnoses (well differentiated through to poorly differentiatied) from both immunocompetent and immunosuppressed patients.

first: Abha

last: Gulati

first: Nikol

last: Mladkova

first: Rifat

last: Hamoudi

first: Karin

last: Purdie

first: Rino

last: Cerio

first: Irene

last: Leigh

last: Proby

first: Catherine

last: Harwood


title: Discovery of consensus gene signature and intermodular connectivity defining self-renewal of human embryonic stem cells

status: Public on Jan 18 2014

first: Yong

last: Kim

address: 10833 Le Conte Ave, 73-022 CHS

summary: Comparison of gene expression signatures in undifferentiated hESCs against differentiated embryoid bodies to identify key signatures defining self-renewal of hESCs.

overall_design: Using H1 and H9 hESC lines, we performed gene expression microarray analysis (Affymetrix Human Genome U133 Plus 2.0 Array) and analyzed the interaction patterns of 54,614 genes using WGCNA in R programming

first: Jeffrey

first: Omar

last: Khalid

first: AmirHosien

last: Namazi

first: Thanh

middle: G

last: Tu

first: Omid

last: Elie

first: Connie

last: Lee


title: Early growth response protein-1 coordinates lipotoxicity-associated placental inflammation: Role in Maternal Obesity

city: Little rock

first: Kartik

last: Shankar

state: AR

address: 1120 Marshall Street, Slot 512-20B

department: Pharmacology and Toxicology

institute: University of Arkansas for Medical Sciences/Arkansas Childrens Nutrition Center

summary: Maternal obesity during pregnancy leads to a pro-inflammatory milieu in the placenta. We conducted a global transcriptomic profiling in BeWo cells following palmitic acid (PA, 500 uM) and/or TNF-alpha (10 ng/ml) treatment for 24 h. Microarray analysis revealed that placental cytotrophoblasts increased expression of genes related to inflammation, stress response and immediate-early factors in response to plamitic acid, TNF-alpha or a combination of both. Our results suggest that fatty acids and inflammatory cytokines induce inflammation in placental cells via activation of JNK-Egr-1 signaling.

first: Jessica

last: Saben

first: Ying

last: Zhong

first: Horacio

last: Gomez-Acevedo

first: Keshari

last: Thakali

first: Sarah

last: Borengasser

first: Aline

last: Andres


title: Prenatal arsenic exposure and the epigenome: altered gene expression profiles in newborn cord blood

city: Chapel Hill

first: Rebecca

middle: Catherine

last: Fry

address: 1213 MHRC

department: Environmental Sciences and Engineering

institute: UNC-Chapel Hill

summary: The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations.

overall_design: We assessed the impact of prenatal exposure to arsenic on genome-wide miRNA expression profiles and their potential influence on gene expression patterns in the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort. This cohort includes residents from Gómez Palacio, located in the state of Durango in the Lagunera region of Northern Mexico. A total of 200 pregnant women residing in Gómez Palacio, State of Durango, Mexico, were recruited at the General Hospital of Gómez Palacio to participate in the BEAR prospective pregnancy cohort. The present study focuses on gene expression profiles and utilizes 38 samples obtained from mother-newborn pairs selected from the larger cohort (n=200). The subcohort was selected to include subjects exposed to varying levels of arsenic as determined by both total arsenic in maternal urine (U-tAs) and inorganic arsenic in drinking water (DW-iAs). Cord blood samples were collected from the newborns immediately after infant delivery. Blood samples were collected using PreAnalytix PaxGene RNA tubes and extracted using the PAXgene RNA Kit, per standard protocol (Qiagen, Valencia, CA). Isolated RNA used for microarray analysis were amplified and labeled using the NuGEN Ovation Pico WTA System V2 and Encore Biotin Module, respectively (NuGEN, San Carlos, CA). RNA isolated from 38 cord blood samples were labeled and hybridized to the Affymetrix Human Gene 2.0 ST Array.

first: Julia

last: Rager

middle: C


title: Human gene expression altered by Chlamydia infection

first: ANYOU

last: WANG

address: Gonda BLDG

department: Human Genetics

summary: Human coronary artery endothelial cells were infected with Chlamydophila pneumoniae. We monitor cellular gene expression profiling altered by life cycle of Chlamydophila pneumoniae using Affymetrix Human Genome U133 Plus 2.0 Array.

overall_design: 5 time points were measured, 5min, 25min, 2h, 24h, 60h after infection

first: Anyou

last: Wang

first: Deborah

last: Dean


title: Identification of chemoresistant genes in hepatocellular carcinoma (HCC)

status: Public on Jan 17 2014

city: Pokfulam

first: Kevin Tak-Pan

last: Ng

address: 21 Sassoon Road

department: Surgery

country: Hong Kong

institute: The University of Hong Kong

summary:
The aim of this study was to identify chemoresistance-associated genes in hepatocellular carcinoma (HCC).
cDNA microarray analysis was performed to compare the mRNA expression profiles of a human metastatic HCC cell line (named MHCC97Low) and its derived chemoresistant sublines including cisplatin resistant subline (named MHCC97L/CisR or C8) and doxorubicin resistant subline (named MHCC97L/DoxR or D5).

overall_design: Total RNAs were extracted from MHCC97Low (97Low as sample name), MHCC97L/CisR (C8 as sample name) and MHCC97L/DoxR (D5 as sample name), and hybridized on Affymetrix microarrays. We planed to identify differential genes between 97Low and C8 (cisplatin resistant genes) as well as to identify differential genes between 97Low and D5 (doxorubicin resistant genes).

first: Kevin

middle: T

first: Kwan

last: Man


title: 17β-estradiol accelerates ovarian tumour progression in vivo though the upregulation of GREB1

status: Public on Jan 20 2014

city: Ottawa

first: Theodore

last: Perkins

address: 501 Smyth Rd.

department: Cellular and Molecular Medicine

institute: Ottawa Hospital Research Institute

summary:
Exogenous 17β-estradiol (E2) accelerates the progression of ovarian cancer in the transgenic tgCAG-LS-TAg mouse model of the disease. We hypothesized that E2 has direct effects on ovarian cancer cells and this study was designed to determine the molecular mechanisms by which E2 accelerates ovarian tumour progression. Mouse ovarian cancer ascites (MASE2) cell lines were derived from tgCAG-LS-TAg mice. Following intraperitoneal engraftment of MASE2 into SCID mice, exogenous E2 significantly decreased the survival time and increased the tumour burden.
Microarray analysis performed on cells derived from mouse ovarian cancer ascites (MASE2)  treated with and without E2 indicated that E2 treatment caused the upregulation and downregulation of genes  involved in cell differentiation, proliferation and migration. In particular, Greb1 that has been also identified as a hormone-responsive gene in breast cances, was upregulated in mouse tumour cells treated with E2.

overall_design: Three biological replicates (MASE2 tumours grown in SCID mice, see growth protocol) were analyzed for both conditions of addition of E2 or placebo.

first: Barbara

last: Vanderhyden


title: Expression changes induced by PTPN1 knockdown in KM-H2 cells

city: Vancouver

first: Christian

last: Steidl

state: BC

address: 675 West 10th Avenue

department: Pathology

institute: BC Cancer Agency

summary: Gene expression data for shRNA PTPN1 knockdown vs. Non-silencing in the classical Hodgkin lymphoma-derived cell line KM-H2

overall_design: A total of 4 samples were analyzed (2 Knockdown vs. 2 Non-silencing). The 2 knockdown and 2 non-silencing samples are technical replicates of each other.

first: Jay

last: Gunawardana


title: Multicellular spheroids treated with the compound VLX600

status: Public on Feb 17 2014

city: Uppsala

first: Mårten

last: Fryknäs

address: Akademiska sjh ingång 61

department: Medical sciencies

country: Sweden

institute: Uppsala university

summary: Microarray based mRNA profiling was used to charactarize the response to the compound VLX600 in cells grown as spheroids. Cells used was colon cancer cells HCT116 and HCT116HIF1a knock-out.

overall_design: We identify the small molecule VLX600 as a drug that is preferentially active against quiescent cells in colon cancer 3-D microtissues. The anticancer activity is associated with reduced mitochondrial respiration, leading to a bioenergetic catastrophe and tumor cell death. VLX600 shows enhanced cytotoxic activity under conditions of nutrient starvation. Microarray based mRNA profiling was used to charactarize the response to the compound VLX600 in cells grown as spheroids. Cells used was colon cancer cells HCT116 and HCT116HIF1a knock-out cells.

first: Marten

last: Fryknas


title: Loss of Lkb1 and Pten Leads to Lung Squamous Cell Carcinoma with Elevated Pdl1 Expression: Epithelial Cells

first: Chunxiao

last: Xu

overall_design: Normal EpCAM+, Kras tumor EpCAM+ and LP tumor EpCAM+ were sorted by FACS, the cells were gating as EpCAM+/CD45-/CD31-

first: Christine

last: Fillmore


title: Expression data from mouse liver

status: Public on Jan 15 2014

city: Singapore

first: Kanaga

last: Sabapathy

state: Singapore

address: 11 Hospital Drive

country: Singapore

institute: National Cancer Centre Singapore

summary: Hepatocellular carcinoma (HCC) is a deadly disease, often unnoticed till the late stages, where treatment options become limited. Thus, there is a critical need to identify early biomarkers for detection of the developing HCC, as well as molecular pathways that would be amenable to therapeutic intervention.  While efforts using human serum and tissues from late stage patients have been undertaken, progress has been limited. We have therefore explored the possibility of utilizing established mouse models for the discovery of biomarkers, as well as to understand in a systematic manner the molecular pathways that are progressively deregulated by the various etiological factors in contributing to HCC formation.  As an initial effort, we have used the Hepatitis B surface antigen (HBsAg) transgenic mice as a hepatitis model, which have been exposed to aflatoxin B1 (AFB1).  In this report, we present the initial findings from a extensive longitudinal study, which confirms the synergistic effect of both these etiological factors, with a gender bias towards male mice.  Tumors from the mouse models were validated both histologically as well as by molecular transcriptome analysis by comparison with human HCCs.  In addition, using these models, we have identified carnitine as a novel biomarker for HCC development, which was again validated using human HCC samples. Conclusion: This study therefore highlights the utility of these mouse models in identifying biomarkers for detection of human HCCs, as well as for the systematic analysis of molecular pathways that are affected by various etiological agents during the progression of HCC from an untransformed hepatocyte, which could provide novel options for targeted therapy.

overall_design: liver obtained from Mus musculus which was intraperitoneally injected with AFB/oil at Day 7 and sacrificed at 15 month age. We intend to compare molecular transcriptome analysis of mouse HCC with human HCCs.

first: Wei

last: Teoh


title: Expression data from AR3 transgenic and wild-type mouse prostates

city: Baltimore

first: Hegang

last: Chen

state: MD

address: 660 West Redwood Street

country: USA

institute: University of Maryland School of Medicine

summary:
We have established AR3 transgenic mouse models with targeted expression of AR3 in the prostate using the ARR2PB promoter.
We have carried out gene expression profiling in AR3 transgenic prostate and wild-type prostate tissues respectively.

overall_design: We performed gene expression profiling in AR3 transgenic prostates to identify differentially expressed genes in the AR3Tg at the age of 4 weeks (n=3),  wild-type littermates (n=3) were used as controls.

first: F

last: Sun

first: Y

last: Qiu


title: Overlapping DNA methylation profile between placentas with trisomy 16 and early-onset preeclampsia

first: Wendy

last: Robinson

address: 950 W 28th Ave

department: Medical Genetics

institute: University of British Columbia

summary: Preeclampsia is one of the leading causes of maternal death worldwide. While the root cause is still unknown, the underlying biology of the disorder is becoming more clear. We recently published a study showing large, significant differences in DNA methylation in 3rd trimester placental samples associated with early-onset preeclampsia (EOPET) compared to controls. In this study, to identify DNA methylation differences associated with preeclampsia that occur early in pregnancy and to further delineate common EOPET-associated differences, we utilized a genetic defect, trisomy 16 (T16), that is predisposing to preeclampsia. We ran T16 placental samples from the 1st trimester (n=5) and 3rd trimester (n=10) against gestational age matched controls on the Illumina Infinium HumanMethylation450 BeadChip. Third trimester samples were from pregnancies with T16 confined to the placenta (confined placental mosaicism 16;CPM16), and consisted of samples that were and were not associated with EOPET (n=5 each). We identified a large number of  DNA methylation differences in CPM16 samples compared to controls using stringent criteria (n=2254;False Discovery Rate <0.01, ->0.15). Several of these differences (11%) overlapped differences observed in chromosomally normal EOPET using similarly stringent criteria (FDR<0.01;->0.125). Isolating EOPET-associated probes produced a similar - distribution amongst CPM16 samples, although samples associated with EOPET showed a tendency towards larger DNA methylation differences. We also identified 262 DNA methylation differences between 1st trimester T16 and 1st trimester controls. Of these, 77 overlapped differences seen in 3rd trimester CPM16. Investigating these 77 T16/CPM16 specific DNA methylation differences, we identified three probes near two genes (ARGHEF37 and JUNB) that were also present as EOPET-associated methylation differences.  In summary, we identified significant overlapping DNA methylation profiles of placentas with T16 and chromosomally normal placentas associated with EOPET. Specific DNA methylation marks within these profiles may be of future clinical utility in early identification of pregnancies susceptible to EOPET.

overall_design: Bisulfite converted DNA from 5 1st trimester trisomy 16 placentas, 5 chromosomally normal 1st trimester placentas, 10 third trimester placentas from confined placental mosaicism placentas and 10 chromosomally normal 3rd trimester placentas

first: John

middle: D

last: Blair

first: Sylvie

last: Langlois

first: Deborah

last: McFadden

middle: P


title: Expression data of overexpression of ABF-1 in SKW cells

city: Taipei

first: Yikai

last: Chiu

address: 128 Academia Road, Section 2, Nankang

institute: Genomics Research Center, Academia Sinica

summary: ABF-1, a bHLH trancriptional repressor expresses in human activated B cells. Overexpression of ABF-1 in a SKW lymphoblastoid cells suppressed IgM production. We used cDNA microarray to identify genes under ABF-1 regulation.

overall_design: SKW cells ectopically expressed ABF-1-GFP or GFP were harvested  for RNA extraction and array hybridization.

first: Yi-Kai

first: I-Ying

last: Lin


title: Prenatal arsenic exposure and the epigenome

first: Rebecca

last: Fry

type:
Non-coding RNA profiling by array
Expression profiling by array

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

overall_design: Refer to individual Series


title: Aberrant DNA methylation reprogramming during iPS cell generation is dependent on the choice of reprogramming factors

status: Public on Jan 16 2014

city: Toronto

first: Daniel

last: De Carvalho

address: 101 College Street, room 9-302

institute: Ontario Cancer Institute

summary: we generate iPSCs from a common fibroblast cell source using either the Yamanaka factors (OCT4, SOX2, KLF4 and MYC) or the Thomson factors (OCT4, SOX2, NANOG and LIN28) and determined their genome-wide DNA methylation profiles. In addition to shared DNA methylation aberrations present in all our iPSCs, we identify Yamanaka-iPSC (Y-iPSCs)-specific and Thomson-iPSCs (T-iPSC)-specific recurrent aberrations.

overall_design: Bisulphite converted DNA from 9 iPS cells derived using Yamanaka factors (OSKM), 6 iPS cells derived using Thompson factors (OSLN), 2 parental fibroblasts and one embrionic ES cell  were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

first: D

first: N

middle: N

last: Batada


title: DLBCL cell-of-origin by gene expression in FFPET

status: Public on Jan 14 2014

city: Bethesda

first: Louis

middle: M.

last: Staudt

address: 9000 Rockville Pike, Bldg 10, Rm 4N114

department: Lymphoid Malignancies Branch

institute: National Cancer Institute

summary: The assignment of diffuse large B-cell lymphoma into cell-of-origin (COO) groups is becoming increasingly important with the emergence of novel therapies that have selective biological activity in germinal center B-cell-like (GCB) or activated B-cell-like (ABC) groups. The LLMPP's Lymph2Cx assay is a parsimonious digital gene-expression (NanoString) based test for COO assignment in formalin-fixed paraffin-embedded tissue (FFPET) routinely produced in standard diagnostic processes. The 20-gene assay was trained using 51 FFPET biopsies; the locked assay was then validated using an independent cohort of 68 FFPET biopsies. Comparisons were made with COO assignment using the original COO model on matched frozen tissue. In the validation cohort the assay was accurate, with only one case with definitive COO being incorrectly assigned, and robust, with >95% concordance of COO assignment between 2 independent laboratories. These qualities, along with the rapid turn-around-time, make Lymph2Cx attractive for implementation in clinical trials and, ultimately, patient management.

overall_design: The retrospective study included RNA extracted from 119 clinical samples.


title: The ets transcription factor ELF5 suppresses the estrogen sensitive phenotype and contributes to antiestrogen resistance in luminal breast cancer. [mouse]

status: Public on Jan 13 2014

city: Darlinghurst

first: Mark

last: Cowley

state: NSW

address: 384 Victoria St.

department: Genome Informatics & Clinical Genomics

country: Australia

institute: Garvan Institute of Medical Research

summary: The ets transcription factor ELF5 specifies the differentiation of mammary progenitor cells to establish the milk-secreting lineage. ER- and poor prognosis basal breast cancers arise from this progenitor cell and these cancers express high levels of Elf5. Knockdown of ELF5 expression in basal breast cancer cell lines, or forced expression in luminal breast cancer cell lines, resulted in reduced cell proliferation. Transcript profiling and chromatin immunoprecipitation revealed that the transcriptional activity of ELF5 specified the gene expression patterns that distinguish basal from luminal breast cancer, including suppression of FOXA1, GATA3 and ER, key estrogen-action genes. Tamoxifen treatment of luminal MCF7 cells upregulated Elf5 expression and cells that acquired resistance to Tamoxifen became dependent on ELF5 for proliferation. ELF5 is a regulator of breast cancer cell proliferation, transcriptionally specifies the basal molecular subtype and is utilised by ER+ breast cancer cells to escape proliferative arrest caused by Tamoxifen.

overall_design: Elf5 was induced via doxycycline treated PyMT mouse tumours, in triplicate

first: Maria

last: Kalyuga

first: David

last: Gallego-Ortega

first: Heather

middle: J

last: Lee

first: Liz

last: Caldon

first: Andrew

last: Stone

first: Stephanie

last: Allerdice

first: Fatima

last: Valdes-Mora

first: Rosalind

last: Launchbury

first: Aaron

last: Statham

first: Nicola

last: Armstrong

first: M

last: Alles

first: Adelaide

last: Young

first: Andrea

last: Egger

last: Au

first: Catherine

last: Piggin

first: Cara

last: Evans

first: Tilman

last: Brummer

first: Warren

last: Kaplan

first: Julia

middle: M

last: Gee

first: Robert

middle: I

last: Nicholson

last: Sutherland

first: Alex

last: Swarbrick

first: Matthew

last: Naylor

first: Susan

last: Clark

first: Jason

middle: S

last: Carroll

first: Christopher

last: Ormandy


title: Therapy-induced PML nuclear body re-formation and p53 activation trigger acute promyelocytic leukaemia cure

status: Public on Jan 11 2014

city: Paris

first: Nabila

last: Elarouci

address: 14 rue Corvisart

department: Recherche

institute: Ligue Nationale contre le Cancer

summary: The therapy-induced PML/RARA catabolism elicits the loss of APL-initiating cell self-renewal through PML NB reformation and P53 activation. These results explain the curative activity of the RA/arsenic combination, the resistance to RA of PLZF/RARA-driven APLs and they raise the prospect that activation of this PML/P53 checkpoint might have therapeutic values in other malignancies.

overall_design: Gene expression profiles of 36 transgenic induced APL and 36 viral transduction APL were hybridized using Affymetrix Mouse Gene 1.0 ST Arrays

first: Julien

last: Ablain

first: Kim

last: Rice

first: Hassane

last: Soilihi

first: Aurélien

last: de Reynies

first: Saverio

last: Minucci

first: Hugues

last: de Thé


title: Microarray of cardiac biventricle from PGC-1a-/-bf/f/MerCre mice

city: Orlando

first: Ola

last: Martin

state: FL

address: 6400 Sanger Rd

institute: Sanford-Burnham Medical Research Institute

summary:
The following abstract from the submitted manuscript describes the major findings of this work.
The metabolic development of high energy-utilizing organs such as the heart involves mitochondrial proliferation at birth followed by a maturation process during the postnatal period. Conditional gene targeting was used in mice to explore the role of the PPARgamma coactivator 1 (PGC-1) coactivators during postnatal development and in adult heart. Marked mitochondrial derangements were observed in hearts of PGC-1a/b-deficient mice during the postnatal period, including fragmentation and elongation associated with the development of a lethal cardiomyopathy. The expression of multiple genes involved in mitochondrial fusion and fission was downregulated in hearts of PGC-1a/b-deficient mice. PGC-la was shown to activate transcription of the mitofusin 1 (Mfn1) gene by coactivating the estrogen-related receptor a (ERRa) upon a highly conserved element.  Surprisingly, PGC-1a/b deficiency did not alter cardiac function or general mitochondrial density and myocyte distribution in adult heart. However, transcriptional profiling and mitochondrial function studies demonstrated that the PGC-1 coactivators are required for full respiratory capacity and high level expression of nuclear- and mitochondrial-encoded genes involved in mitochondrial energy transduction and oxidative phosphorylation pathways in adult heart. These results unveil distinct developmental stage-specific transcriptional programs involved in the maturation and maintenance of mitochondria.

overall_design: RNA from five PGC-1a-/- and five PGC-1a-/-bf/f/MerCre mice was analyzed.

first: Ling

last: Lai

first: Daniel

last: Kelly


title: Pancreatic cancer-induced cachexia syndrome

status: Public on Jan 10 2014

city: Quebec

first: Ezequiel

last: Calvo

state: Quebec

address: 2705 Boul. Laurier

department: Molecular Endocrinilogy

institute: CRCHUL

summary: Cancer cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and it is one of the most frequent causes of death. Severe wasting accounts for more than 80% in patients with advanced pancreatic cancer. Here we wanted to define, by using an microarray approach and the Pdx1-cre;LSL-KrasG12D;INK4a/arffl/fl, the pathways involved in muscle, liver and white adipose tissue wasting.

overall_design: The aim of our work was to characterize as extensively as possible the pathways activated by the pancreatic cancer-induced cachectic tissues. For this purpose, we generated and compared genome-wide expression profiles of white adipose tissue, skeletal muscle and liver, from Pdx1-cre;LSL-KrasG12D;INK4a/arffl/fl and LSL-KrasG12D;INK4a/arffl/fl mice at 10 weeks-old. Tissue samples by triplicate was obtained from liver, muscle and adipose tissues in both groups, controls and cachectic mice. Total RNA samples was processed and profiled on Affymetrix Mouse Gene 1.0 ST arrays as previously described (Cano et al, 2012)

first: Marine

last: Gilabert

first: Tewfik

last: Hamidi

first: Vincent

last: Moutardier

first: Olivier

last: Turrini

first: Juan

last: Iovanna


title: Screening target genes of miR-100 in MGC-803 and SK-BR-3 cells

status: Public on Jan 09 2014

city: shanghai

first: qian

last: jin

address: libing road

institute: MSP

summary: We tried to find the target genes of miR-100 in MGC-803 and SK-BR-3 cells, thus we uesd specific miR-100 inhibitor to knock down the level of miR-100 in the cells, with this condition, we used this mRNA microarray to find the genes whose amount changed. and they may be the target genes that miR-100 mediated.

overall_design: Total of four chips, MGC-AMO, MGC-NC, SK-AMO, SK-NC. MGC and SK represents MGC-803 and SK-BR-3 cells respectively.  AMO is the specific miR-100 inhibitor and NC is negative control.

first: Yi

last: Gong


title: G9a-dependent gene expression in mouse AML cells

status: Public on Jan 08 2014

city: Montreal

first: Bernhard

last: Lehnertz

state: QC

address: 2950 Chemin polytechnique

department: IRIC

institute: University of Montreal

summary:
The methyltransferase G9a was found to play a role in the disease progression of a murine model of AML.
Mouse HSPCs were transformed with HoxA9/Meis1 and treated with G9a/GLP inhibitor UNC0638.

overall_design: We used microarrays to detail the global program of gene expression that depends on the methyltransferase activity of G9a in murine AML cells.

first: Fabio

last: Rossi


title: Smoking and Obesity Related Molecular Alterations in Clear Cell Renal Cell Carcinoma

city: Jacksonville

last: Serie

state: Florida

address: 4500 San Pablo Rd

institute: Mayo Clinic

summary: Both cigarette smoking and obesity have been implicated in increased risk of clear cell renal cell carcinoma (ccRCC); however, there are limited data   regarding the molecular mechanisms that underlie these associations.  We used a multi-stage design to identify and validate specific molecular targets that are associated with smoking or obesity-related ccRCC.

overall_design:
The data deposited herein are comprised of two batches of samples that were processed at two different time periods (please see Supplementary Data in Eckel-Passow et al. Carcinogenesis first published online December 28, 2013; doi:10.1093/carcin/bgt485).  The first batch of samples consisted of 12 obese subjects and 13 non-obese subjects; all of whom were self-reported never-smokers.  Each of the 12 obese subjects had  microarray data available on both the patient-matched tumor and adjacent-normal tissues.  All of the 13 non-obese subjects had microarray data available on the tumor tissue; however, only 9 of these 13 also had microarray data available on the patient-matched adjacent-normal tissue.  The second batch of samples consisted of 16 self-reported smokers and 19 self-reported never smokers; all of whom were non-obese.   This second batch of samples also contained 7 subjects who were obese and self-reported smokers.  All subjects in the second batch had microarray data available on both the patient-matched tumor and adjacent-normal tissues.  Lastly, two of the 13 patients in batch 1 were replicated in batch 2; both were non-obese and a non-smoker.
These two technical replicates (two tumor samples and two normal samples) were included during normalization but removed prior to analysis.  The cel files are
Par007U133Plus2.0.CEL
Par008U133Plus2.0.CEL
Par041U133Plus2.0.CEL
Par042U133Plus2.0.CEL
The metadata "duplicate" column can also be used to exclude these samples.

first: Jeanette

last: Eckel-Passow