title: Transcriptome partitioning for mRNA translation in hypoxia

city: Berlin

first: Michael

last: Fähling

address: Charitéplatz 1

department: Institut für Vegetative Physiologie

institute: Charité - Universitätsmedizin Berlin

summary: Protein synthesis belongs to the most energy consuming processes in the cell. Lowering oxygen tension below normal (hypoxia) causes a rapid inhibition of global mRNA translation due to the decreased availability of energy. Interestingly, subsets of mRNAs pursue active translation under such circumstances. In human fibrosarcoma cells (HT1080) exposed to prolonged hypoxia (36 h, 1% oxygen) we observed that transcripts are either increasingly or decreasingly associated with ribosomes localized at the endoplasmic reticulum (ER). In a global setting it turned out that only 31% of transcripts showing elevated total-RNA levels were also increasingly present at the ER in hypoxia. These genes, regulated by its expression as well as its ER-localization, belong to the gene ontology’s “hypoxia response”, “glycolysis” and “HIF-1 transcription factor network” supporting the view of active mRNA translation at the ER during hypoxia. Interestingly, a large group of RNAs was found to be unchanged at the expression level, but translocate to the ER in hypoxia. Among these are transcripts encoding translation factors and >180 ncRNAs. In summary, we provide evidence that protein synthesis is favoured at the ER and, thus, partitioning of the transcriptome between cytoplasmic and ER associated ribosomes mediates adaptation of gene expression in hypoxia.

overall_design: Human fibrosarcoma HT1080 cells were cultured for 36 h under control/atmospheric (21% O2, 5% CO2, 37 °C) or hypoxic (1% O2, 5% CO2, 37°C) conditions. Total RNA (representing expression level) and ER (endoplasmatic reticulum)-RNA (representing transcript localization at ER) was isolated for both conditions. Pooled RNA samples from 5 independent biological experiments were used for microarray analysis.

first: Jonas

last: Staudacher

first: Stefanie

middle: J

last: Ujvari

first: Bertram

last: Klinger

first: Dirk

last: Ostareck

first: Isabel

last: Naarmann-de Vries

first: Pontus

last: Persson

first: Antje

last: Ostareck-Lederer

first: Mumtaz

last: Kasim

first: Edgar

last: Benko


title: Effective sorafenib treatment response in a panel of genomically-characterized malignant peripheral nerve sheath tumor orthoxenograft models

status: Public on Apr 15 2015

city: Badalona

first: Bernat

last: Gel Moreno

state: Barcelona

address: Ctra. de Can Ruti, camí de les escoles, s/n

department: Hereditary Cancer Program

country: Spain

institute: Institut de Medicina Predictiva i Personalitzada del Càncer

summary:
Background: Malignant peripheral nerve sheath tumors (MPNST) are soft-tissue sarcomas that can arise either sporadically or in association with neurofibromatosis type 1 (NF1). These aggressive malignancies confer poor survival, with no effective therapy available.
Methods: We generated five patient-derived MPNST orthoxenograft models (three NF1-related and two sporadic) and performed an exhaustive histological and molecular characterization of primary MPNSTs and their corresponding orthoxenografts. Finally, orthoxenografts models were used as an in vivo pre-clinical platform to test several treatment strategies.
Results: MPNST orthoxenografts recapitulate the histopathological properties and preserve the genomic and transcriptomic status of their parental primary tumors. Additionally, they mimic distal dissemination properties in mice. Compatible with an origin in a catastrophic event and subsequent stabilization, MPNSTs contained highly altered genomes that remained remarkably stable in orthoxenograft establishment and along passages. Although preliminary, the results presented here point to clear differences between NF1-associated and sporadic MPNSTs. In accordance, mutation frequency in sporadic MPNSTs was an order of magnitude higher than in NF1-associated MPNSTs and unsupervised cluster analysis and principal component analysis (PCA) using a MPNST signature perfectly divided the samples between NF1 and sporadic MPNST. Finally, different therapeutic approaches tested in the validated orthoxenograft MPNST models, reveal that sorafenib, or in combination with doxorubicin or rapamycin caused a great tumor reduction in all models.
Conclusion: The development of a well-characterized and standardized preclinical model for MPNSTs has laid the foundations for evaluating novel therapeutic strategies in the clinical setting. Moreover, results obtained strongly support the clinical evaluation of Sorafenib in this subset of patients.

overall_design: Primary MPNSTs were implanted in the sciatic nerve of nude mices to create orthoxenograft MPNST models. Several orthoxenograft passages were created. The primary tumor (when available) and passages 1 and 4 were selected for gene expression profiling to demonstrate that the orthoxenografts closely resemble their primary tumors and are stable along xenograft passages.

first: Joan

last: Castellsagué

last: Gel

first: Juana

last: Fernández-Rodríguez

first: Roger

last: Llatjós

first: Ignacio

last: Blanco

first: Yolanda

last: Benavente

first: Diana

last: Pérez-Sidelnikova

first: Javier

last: García-del Muro

last: MariaViñals

first: Rafael

last: Valdés-Mas

first: Ernest

last: Terribas

first: Adriana

last: López-Doriga

first: Miguel

middle: A

last: Pujana

first: Gabriel

last: Capellá

first: Xose

middle: S

last: Puente

first: Eduard

last: Serra

first: Alberto

last: Villanueva

first: Conxi

last: Lázaro


title: Growth inhibition by Merlin expression correlates with a cross-tissue transcriptional signature

status: Public on Apr 01 2015

city: London

first: Stephen

last: Henderson

address: Paul O'Gorman Building

department: Cancer Institute

country: United Kingdom

institute: UCL

summary:
We have found a broad case of tumour suppressor hypersensitivity for Merlin in cancer: Merlin expression in Merlin deficient cells (but not Merlin wild type cells) strongly suppresses proliferation regardless of tumour type or of additional somatic mutations.
To study how Merlin selectively induced growth arrest in Merlin-deficient cells, global gene expression regulation by Merlin was examined by microarray in a set of four cell line pairs derived from different tumour types

overall_design: Four Merlin-deficient and four Merlin wild type cell lines derived from four different tissues/tumour types (meninges, thyroid, kidney, breast) were infected with pLEX lentiviruses (Open Biosystems) expressing either wt Merlin or Merlin L46R (a tumour-derived loss-of-function mutant, used as a control). 24 hours after infection, fresh media containing 2.5ug/ml puromycin was added (drug selection) and cells grown for a further 24 hours, i.e. cells were harvested 48hour after infection. RNA was analyzed using GeneChip Human Gene 2.0 ST arrays (Affymetrix). n=2 for Merlin-deficient cell lines; n=1 for Merlin wt cell lines

first: Pablo

last: Rodriguez-Viciana

first: Anne

last: Rohrig


title: Gene expression signature regulated by cell density and Merlin/NF2 knockdown in HMLE cells

summary:
Merlin has been implicated in contact-dependent inhibition of proliferation
To define genes regulated by Merlin and study their relationship to cell density-dependent gene expression, microarray experiments were performed after Merlin depletion in HMLE cells at both high and low cell densities. HMLE are non-transformed immortalized human mammary epithelial cells (Elenbaas et al., Genes Dev 15,  2001)

overall_design: HMLE cells were transfected with NF2 or scramble (control) siRNAs. 2 days later medium was changed (dense) or cells seeded in sparse conditions and RNA isolated the day after (3 days after siRNA transfection)


title: Transcriptional control by Merlin of contact inhibition and tissue homeostasis

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

overall_design: Refer to individual Series


title: Expression arrays of ANGPTL2 treated CD34 cells

status: Public on Mar 16 2015

city: New York

first: Richard

middle: Mark

last: White

state: NY

address: 1275 York Avenue MB 424

department: Cancer Biology & Genetics

country: USA

institute: Memorial Sloan Kettering Cancer Center

summary: ANGPTL2 is a protein in the angiopoietin-like protein family and plays a role in hematopoietic and vascular physiology.  This study examined the effects of ANGPTL2 on CD34+ human hematopoetic progenitor cells.

overall_design: 6 samples total: 3 control samples plus 3 samples treated for 1 hour with ANGPTL2 (1ug/ml)

first: Leonard

last: Zon

first: Michelle

last: Lin


title: SNP array of human neuroblastoma cell lines SH-SY5Y, SH-EP and SK-N-SH

status: Public on Mar 03 2015

city: Essen

first: Sven

last: Lindner

address: Hufelandstraße 55

country: Germany

institute: University Hospital Essen

summary: TERT promoter muatations occur frequently in tumors of various origin. We here accessed the frequency of TERT pomoter mutations in 131 human primary neuroblastomas and 20 human neuroblastoma cell lines. No TERT promoter mutations were found in the 131 primary neuroblastomas. However, in the three cell lines SH-SY5Y, SH-EP and SK-N-SH  a TERT promoter mutation was detected. Sanger sequencing indicated a homozygous mutation. To confirm loss of heterozygosity (LOH) we performed Affymetrix CytoScanHD SNP arrays. Indeed LOH could be confirmed.

overall_design: SNP arry experiments were performed according to the standard protocol for Affymetrix CytoScanHD arrays (Affymetrix, Santa Clara). Briefly, a 250 ng sample of genomic DNA was digested with NspI, ligated to adaptors, amplified by PCR, fragmented and biotin-labeled. The labeled samples were hybridized to Affymetrix CytoscanHD arrays, followed by washing, staining and scanning in the Affymetrix GeneChip Scanner 3000. Analysis was performed using the Affymetrix Chromosome Analysis Suite v2.1.

first: Johannes

middle: H

last: Schulte


title: CNV and ROH analysis of patients with a region of triplication followed by a terminal region of ROH and their parental samples

city: Nijmegen

first: Rolph

last: Pfundt

address: Geert Grooteplein Zuid 6

department: Genetics

country: Netherlands

institute: RUNMC

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

summary: These samples include 4 patients with a triplication/ROH combination on: (1) chromosome 6, (2) chromosom 9, (3) chromosome 10, (4) chromosome 14

overall_design: All arrays contain single hybridisations of either patient or parental samples

first: Claudia

middle: M

last: Carvalho Fonseca


title: Inhibition of ABCB1 Overcomes Cancer Stem Cell-like Properties and Acquired Resistance to MET inhibitor in Non-Small Cell Lung Cancer

status: Public on Mar 07 2015

city: Tokyo

first: Teppei

last: Sugano

address: Sendagi, Bunkyo-ku

country: Japan

institute: Graduate School of Medicine,

summary: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations have shown a dramatic response to EGFR inhibitors (EGFR-TKI). EGFR T790M mutation and MET amplification have been recognized as major mechanisms of acquired resistance to EGFR-TKI. Therefore, MET inhibitors have recently been used in NSCLC patients in clinical trials. In this study, we tried to identify the mechanism of acquired resistance to MET inhibitor. We analyzed the antitumor effects of two MET inhibitors, PHA-665752 and crizotinib, in 10 NSCLC cell lines. EBC1 cells with MET amplification were the only cells that were sensitive to both MET inhibitors. We established PHA-665752-resistant EBC1 cells, namely EBC1-R cells. EBC1-R cells showed overexpression of ATP-binding cassette sub-family B member 1 (ABCB1) as well as phosphorylation of MET. EBC1-R cells grew as cell spheres that exhibited cancer stem cell-like (CSC) properties and epithelial mesenchymal transition (EMT). The levels of two miRNAs, miR-374a and miR-138 which targeted ABCB1, were decreased in EBC1-R cells. ABCB1 siRNA and ABCB1 inhibitor elacridar could reduce sphere numbers and suppress EMT. Elacridar could also reverse the resistance to PHA-665752 in EBC1-R cells. Our study demonstrated that ABCB1 overexpression which was associated with CSC properties and EMT was involved in the acquired resistance to MET inhibitor. Inhibition of ABCB1 might be a novel therapeutic strategy for NSCLC patients with acquired resistance to MET inhibitor.

overall_design: To search resistant mechanisms of met inhibitor in EBC1-R cell, we compared EBC-1 cell and EBC1-R cell.

first: Masahiro

last: Seike

first: Rintaro

last: Noro

first: Chie

last: Soeno

first: Mika

last: Chiba

first: Shinji

last: Nakamichi

first: Nobuhiko

last: Nishijima

first: Masaru

last: Matsumoto

first: Akihiko

last: Miyanaga

first: Kaoru

last: Kubota

last: Gemma


title: Fibroblast VEGF-receptor 1 expression as molecular target in periodontitis

status: Public on Mar 11 2015

city: Los Angeles

first: Masafumi

last: Horie

address: 2011 Zonal Ave

institute: University of Southern California

summary: To identify gene expression profiles in those periodontitis-associated fibroblasts (PAFs) versus normal gingival fibroblasts to determine their molecular repertoire, and exploit it for therapeutic intervention.

overall_design: We collected RNA from 4 paired PAF and non PAF from patients with periodontitis

first: Yoko

last: Yamaguchi

first: Mitsuhiro

last: Ohshima

first: Yoshimitsu

last: Abiko

first: Asayo

last: Imaoka

first: Akira

last: Saito


title: HUVEC Gene Regulation by Histidine-Rich Glycoprotein

status: Public on Mar 12 2015

city: Uppsala

first: Lena

last: Claesson-Welsh

state: Uppsala

address: Dag Hammarskjölds v 20

department: Immunology, Genetics and Pathology

country: Sweden

institute: Uppsala University

summary: HRG is a 75kDa heparin-binding protein non to extert gene regultaion changes on macropahges. To assess the effect of HRG on Enodothelial Cell gene regulation Human Umbilical Vein Endothelial Cells (HUVECs) were treated with Histidine-Rich Glycoprotein (HRG) 24 hour treatment with HRG. and examined for gene regulation changes versus untreated HUVECs after 6 and

overall_design: A total of 8 samples were analysed. HUVECs were treated with HRG (1ug/ml) or PBS (control) in culture for 6 and 24 hours after treatment in duplicate.

first: Francis

last: Roche

first: Sonia

last: Tugues


title: A unifying gene signature for adenoid cystic cancer identifies parallel MYB-dependent and MYB-independent therapeutic targets

status: Public on Mar 13 2015

city: Houston

first: Nicholas

last: Navin

state: tx

address: 6767Bertner AVE

institute: UT MD Anderson

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

summary: MYB activation is proposed to underlie development of adenoid cystic cancer (ACC), an aggressive salivary gland tumor with no effective systemic treatments. To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of 12 ACC with matched normal tissues, and compared these data with 14 mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top-scoring gene (18-fold induction), however we observed the same signature in ACC without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among our 12 cases and 3 from public databases) with negligible MYB expression that retained the same ACC mRNA signature including over-expression of extracellular matrix (ECM) genes. Integration of this signature with somatic mutational analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM elements including the VCAN/HAPLN1 complex. We observed that forced MYB-NFIB expression in human salivary gland cells alters cell morphology and cell adhesion in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC tumor culture. In summary, we identified a unique ACC signature with parallel MYB-dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a potential target.

platform_organism:
Homo sapiens
synthetic construct

overall_design: This study included 8 MYB-NFIB fusion positive adenoid cystic cancer (ACC); 4 MYB-NFIB fusion negative adenoid cystic cancer tumors; and 12 matched normal samples respectively. The fusion status was pre-defined using RT-PCR methods. This study includes both miRNA chip and mRNA array expression assays that were performed for the same set of tumors.


title: A unifying gene signature for adenoid cystic cancer identifies parallel MYB-dependent and MYB-independent therapeutic targets (mRNA)

overall_design: A total 12 human salivary gland adenoid cystic cancer and 12 mathced normal adjacent tissues. The 12 tumor samples contains 8 MYB-NFIB fusion positive tumor samples and 4 MYB-NFIB fusion negative samples. One of the 4 fusion negative tumors did not have high MYB expression. This is a mRNA whole exome expression assay.

first: Ruli

last: Gao

first: Chunxia

last: Cao

first: Min

last: Zhang

first: Lopez

last: Maria-Cecilia

first: Yuanqing

last: Yan

first: Zirong

last: Chen

first: Yoshitsugu

last: Mitani

first: Li

first: Maria

last: Zajac-Kaye

first: Bin

last: Liu

first: Lizi

last: Wu

first: Rolf

last: Renne

first: Henry

middle: V

last: Baker

first: Adel

last: El-Naggar

first: Frederic

last: Kaye


title: Gene Networks Specific for Innate Immunity Define Post-traumatic Stress Disorder [Affymetrix]

status: Public on Feb 27 2015

first: Michael

last: Breen

address: 1468 Madison Ave

department: Depts. of Psychiatry, Genetics and Genomic Sciences

institute: Ichan School of Medicine at Mount Sinai

summary:
The molecular factors involved in the development of Post-traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network-based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. These findings provide novel insights for early preventative measures and advanced PTSD detection, which may lead to interventions that delay or perhaps abrogate the development of PTSD.
We used microarrays to characterize both prognostic and diagnostic molecular signatures associated to PTSD risk and PTSD status compared to control subjects.

overall_design: Peripheral blood leukocytes gene expression was subject to transcriptional analysis for 48 service members both prior-to and following deployment to conflict zones. Half of the subjects returned with Post-traumatic Stress Disorder (PTSD), while the other half did not.

first: Adam

middle: X

last: Maihofer

first: Stephen

last: Glatt

first: Daniel

last: Tylee

first: Sharon

middle: D

last: Chandler

first: Ming

middle: T

last: Tsuang

first: Victoria

middle: B

last: Risbrough

first: Dewleen

middle: G

last: O'Connor

first: Christopher

last: Woelk

first: Caroline

last: Nievergelt


title: Expression data from renal cancer xenograft tumor treated with sunitinib or vehicle

status: Public on Mar 10 2015

city: Kyoto

first: Shibasaki

last: Noboru

address: 54 Shogoinkawahara-cho Sakyo-ku

department: Urology

institute: Kyoto University

summary:
We established 3 types of primary xenograft models (KURC;Kyoto University Renal Cancer-1,2,3) derived from human renal cell carcinoma tissues, and 40 mg/day of sunitinib was orally administered.
We performed microarray analysis to compare the gene expression profile of sunitinib-treated primary xenograft tumors (sensitive or resistant status) with that of vehicle-treated.

overall_design: Total RNA was extracted from KURC1,2,3 xenograft tumors treated with sunitinib or vehicle. Forty mg/day of sunitinib was orally administered once a day, and KURC1 and KURC3 developed resistance to sunitinib.

first: Noboru

last: Shibasaki


title: Comparative gene expression profiles of immune inhibitory and non-inhibitory melanoma cell lines

status: Public on Mar 01 2015

city: Doha

first: Francesco

middle: Maria

last: Marincola

address: Al Nasr Tower, AL Corniche Street, PO Box 26999

country: Qatar

institute: Sidra Medical and Research Center

summary: Dysfunction in type I interferon (IFN) signaling occurs in patients with stage II or more advanced cancer. After screening the effects of a panel of 12 melanoma cell lines on PBMCs of healthy volunteers of IFNalpha signal pathway, two groups of melanoma cell lines could be identified one with stronger suppression (low pSTAT-1 group) than the other (high pSTAT-1 group). Comparative global gene expression between two groups identified 6771 differential expression genes. This gene list indicated down regulation of IFNalpha signal in immune suppressive melanoma cells. To evaluate this gene list for predictive power on IFNalpha signal modulatory function, we analyzed gene expression 41 independent melanoma cell lines and heat map clusters these cell lines into two groups, one with strong immune suppressive function and other with less effect.

overall_design: Fifty-three melanoma cell lines were analyzed with twelve technical repeats.


title: Gene expression profiling of human neuroblastoma BE(2)-C cells with MEIS2 depletion

city: Augusta

first: Justin

last: Choi

state: GA

address: 1410 Laney Walker Blvd.

department: Cancer Center

institute: Georgia Regents University

summary: MEIS2 has an important role in development and organogenesis, and is implicated in the pathogenesis of human cancer. The molecular basis of MEIS2 action in tumorigenesis is not clear. Here, we show that MEIS2 is highly expressed in human neuroblastoma cell lines and is required for neuroblastoma cell survival and proliferation. Depletion of MEIS2 in neuroblastoma cells leads to M phase arrest and mitotic catastrophe, whereas ectopic expression of MEIS2 markedly enhances neuroblastoma cell proliferation, anchorage-independent growth, and tumorigenicity. Gene expression profiling reveals an essential role of MEIS2 in maintaining the expression of a large number of late cell cycle genes, including those required for DNA replication, G2-M checkpoint control and M phase progression. Importantly, we identify MEIS2 as a transcription activator of the MuvB-BMYB-FOXM1 complex that functions as a master regulator of mitotic gene expression. Further, we show that FOXM1 is a direct target gene of MEIS2 and is required for MEIS2 to upregulate mitotic genes. These findings link a development gene to the control of cell cycle progression and suggest that high MEIS2 expression is a molecular mechanism for high expression of mitotic genes that is commonly observed in cancers of poor prognosis.

overall_design: Affymetrix microarray assays were performed according to the manufacturer's directions on total RNA isolated from three independent samples of BE(2)-C cells infected with lentiviruses expressing either shGFP or shMEIS2-43 for 48 hours.

first: Han-Fei

last: Ding

first: Yunhong

last: Zha


title: Transcriptomic Analysis of Non-small Cell Lung Cancer Stem Cells

city: Kepala Batas

first: Badrul

middle: Hisham

last: Yahaya

state: Penang

address: Bertam, Kepala Batas

department: Advanced Medical & Dental Institute

country: Malaysia

institute: Advanced Medical and Dental Institute

summary:
This study was designed to understand the transcriptomic composition and the biological functions of cancer stem cells isolated from non-small cell lung cancer line (NSCLC)
Putative lung cancer stem cells were isolated from cancer cell lines based on expression of known stem cell surface markers: CD166, CD44 and EpCAM using the Fluorescence Activated Cell Sorter (FACS).

overall_design: Affymetrix microarray were performed on cancer stem cells isolated from normal lung epithelial cells and lung cancer cell lines (A549 and NCI-H2170) using GeneChip Human Gene 1.0 ST array. The normal putative stem cells isolated from normal primary human bronchial/trachial epithelial cell line (PHBEC) was serve as control. Putative cancer stem cells isolated from A549 and NCI-H2170 cell lines are the treatment group. Each sample was performed in triplicate and total number of samples are five (n=5)

first: Norashikin

last: Zakaria


title: Adipocyte-derived Exosomal miRNAs from Visceral Adipose Tissue: A Novel Mechanism for Obesity-Related Disease

city: Washington

first: Robert

last: Freishtat

state: DC

address: 111 Michigan Avenue NW

department: Center for Genetic Medicine

institute: Children's National Medical Center

summary: Affymetrix miRNA 3.0 array profiling of adipocyte-derived exosomes from obese and lean human subjects. We used miRNA arrays to profile exosomes shed from obese and lean human visceral fat that was cultured for 60 minutes.

overall_design: Human obese and lean visceral fat was surgically acquired, dissected, and promptly cultured for 60 minutes. We used the culture supernatants for exosome purification and isolation using ExoQuick-TC Precipitation Solution.

first: Sarah

middle: C

last: Ferrante

first: Evan

last: Nadler


title: Identification of differentially expressed genes in LBH589-treated cells

status: Public on Mar 02 2015

city: Duarte

first: Shiuan

last: Chen

state: CA

address: 1500 E Duarte Rd

department: Surgical Research

institute: City of Hope

summary: To identify the targets of LBH589 treatment, we compared gene expression profiles in three different types of human cancer cell lines (H295R, HeLa and MCF-7her2) with and without LBH589 treatment.  Affymetrix microarray analysis was performed to determine changes in gene expression that are unique to LBH treatment.

overall_design: LBH-treated cell lines received 50 nM of LBH589 for 24 hours. DMSO and LBH treatments are in triplicate.

first: S


title: Studying the effects of the TEN1-ICD on transcriptional regulation

status: Public on Feb 04 2015

city: Basel

first: Tim

last: Roloff

address: Maulbeerstrasse 66

department: Functional Genomics

country: Switzerland

institute: FMI

summary: Teneurins are large type II transmembrane proteins that are necessary for the normal development of the central nervous system (CNS). While many studies highlight the significance of teneurins, especially during development, there is only limited information known about the molecular mechanisms of function. Previous studies have shown that the N-terminal intracellular domain (ICD) of teneurins can be cleaved at the membrane and subsequently translocates to the nucleus where it can influence gene transcription. Target genes as well as mechanisms have yet to be elucidated, and thus we are investigating the transcriptional activity of the human teneurin-1 ICD in this study.

overall_design: For the whole transcriptome analysis of TEN1-ICD overexpression, we used a modified and improved tet-system. Two separate vectors are required to make the cell line stable. One contains the tet-activating domain fused to a glucocorticoid binding domain (GBD). The other contains the tetO operator sequences directly upstream of a CMV promoter and the gene to be overexpressed. BS149 cells were first transfected with pirtetR-GBD and made stable by Puromycin selection, and then after further transfection with either ptetO-eGFP-His (negative control) or ptetO-TEN1-ICD-eGFP-His by Hygromycin selection. The stable BS149 cell lines were split into three 10 cm Petri dishes each. The triplicate cell lines were cultured once before induction with Dexamethasone and Doxycycline. The overexpressing cells were then FACS-sorted directly into RLT lysis buffer (Qiagen) at a 3:1 volume ratio of lysis buffer to cells in PBS, 24 h post-induction.

first: Jonas

last: Schöler

first: Stéphane

last: Thiry

first: Jacqueline

last: Ferralli

first: Ruth

last: Chiquet-Ehrismann


title: Comparing the effects of MITF on transcriptional regulation to the TEN1-ICD

summary: We identified histidine triad nucleotide binding protein 1 (HINT1) as a human teneurin-1 ICD interaction partner in a yeast-2 hybrid screen. This interaction was confirmed in human cells, where HINT1 is known to inhibit the transcription of target genes by directly binding to transcription factors at the promoter. In a whole transcriptome analysis of BS149 glioblastoma cells overexpressing the teneurin-1 ICD, several microphthalmia-associated transcription factor (MITF) target genes were found to be up-regulated. Interestingly, MITF is one of the transcription factors inhibited by HINT1. Thus, we directly compare the transcriptomes of MITF versus TEN1-ICD overexpressing BS149 cells in this study, in order to reveal any co-regulated genes.

overall_design: For the whole transcriptome analysis of MITF, cells were transiently transfected in triplicates with either, pcDNA3.1-RFP-HA (negative control) or pcDNA3.1-MITF-RFP-HA. The overexpressing cells were then FACS-sorted directly into RLT lysis buffer (Qiagen) at a 3:1 volume ratio of lysis buffer to cells in PBS, 24 h post-transfection.


title: Expression data of pediatric B-cell acute leukemias

status: Public on Feb 23 2015

city: San Francisco

first: Seung-Tae

last: Lee

address: 1450 3rd Street

institute: UCSF

summary:
We investigated DNA methylomes of 227 pediatric B-cell acute lymphoblastic leukemias (B-ALLs) using whole-genome bisulfite sequencing and high-definition microarrays, along with RNA expression profiles.
The current study identified a link between DNA methylome of B-cell acute lymphoblastic leukemias (B-ALLs) and embryonic stem cell (ESC) bivalency, through which tumor cells can mimic the pluripotency of ESCs.

overall_design: A total of 231 pediatric patients with B-ALL were utilized from the California Childhood Cancer Study. After informed consent, bone marrow specimens packed with leukemic blasts were obtained in each patient. Expression and methylation data of purified Pre-B cells in four developmental stages were retrieved from our previous study (Lee et al., Nucleic Acids Res 2012).

first: Joseph

middle: L

last: Wiemels


title: 5Z-7-Oxozeanol inhibits the effect of TGFB1 on human gingival fibroblasts

status: Public on Feb 26 2015

first: David

middle: E

last: Carter

state: ON

address: 1151 Richmond Street North

department: London Regional Genomics Centre

country: Canada

institute: Robarts Research Institute

summary: Microarray analysis was used to show that in gingival fibroblasts essentially all TGFB1 responsive genes were blocked by TAK inhibition

overall_design: Affymetrix Human Gene 1.0 ST arrays were used to identify differential gene expression changes bewteen samples.

first: Hanna

last: Kuk

first: James

last: Hutchenreuther

first: Hannah

last: Murphy-Marshman

first: Andrew

last: Leask


title: Expression data for tet-on inducible mouse p53 stable line in H1299 cells

status: Public on Jan 31 2015

first: Le

last: Jiang

address: 1130 St. Nicholas Ave

institute: Columbia University

summary: In order to identify novel genes regulated by p53, stable line containing tet-on inducible p53 construct was generated and used for gene expression analysis.

overall_design: Tet-on p53 inducible stable line was induced by doxycyclin for 24 hours before total RNA was extracted for array analysis.

first: Wei

last: Gu


title: Expression data from HeLa cells overexpressing AK125393

status: Public on Feb 19 2015

city: Jerusalem

first: Sharon

last: Zeligson

address: 12 Shmuel Bayit St.

department: Medical Genetics

country: Israel

institute: Shaare Zedek Medical Center

summary:
Expression of RAD51, a crucial player in homologous recombination (HR) and DNA double-strand break (DSB) repair, is dysregulated in human tumors, and can contribute to genomic instability and tumor progression. To further understand RAD51 regulation we functionally characterized a long non-coding (lnc) RNA, AK125393, dubbed TODRA (Transcribed in the Opposite Direction of RAD51), transcribed 69bp upstream to RAD51, in the opposite direction.
TODRA overexpression in HeLa cells induced expression of TPIP, a member of the TPTE family which includes PTEN. Similar to PTEN, we found that TPIP co-activates E2F1 induction of RAD51.

overall_design: HeLa cells were transfected with either an empty vector or an AK1253893 minigene. RNA was extracted from duplicates of each experiment and hybridized to affymetrix microarray.

first: Inbal

last: Gazy

last: Zeevi

first: Paul

last: Renbaum

first: Lital

last: Eini

first: Dana

last: Bashari

first: Yoav

last: Smith

first: Amnon

last: Lahad

first: Michal

last: Goldberg

first: Doron

last: Ginsberg

first: Ephrat

last: Levy-Lahad


title: TEN1-ICD studies

first: Tim

last: Roloff

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

overall_design: Refer to individual Series


title: Expression data from neural crest cells and neural crest cell-derived MSCs from human pluripotent stem cells

status: Public on Feb 11 2015

city: kyoto

first: Junya

last: Toguchida

address: 53 kawahara-cho, shogoin

department: Center for iPS Cell Research and Application(CiRA)

summary: We developed simple, robust, efficient, and serum-free/feeder-free induction protocol for neural crest cells from human pluripotent stem cells. To characterize the hNCCs and hNCC-derived MSCs, we performed gene expression profiling experiments.

overall_design: Comparison of gene expressions among hiPSCs, hESCs, hNCCs and hNC-MSCs

first: J

first: M

last: Ikeya


title: Mycobacterium tuberculosis Chaperonin 60.1 has Bipolar Effects on Human peripheral blood-derived Monocytes

status: Public on Feb 17 2015

city: London

first: Ana

last: Cehovin

state: United Kingdom

address: Exhibition Road

department: Centre for Molecular Microbiology and Infection

institute: Imperial College London

summary:
Chaperonin 60 (Cpn60) is a prototypic molecular chaperone essential for cellular function due to its protein folding actions.  However, over the past decade it has been established that Cpn60 can be released by human cells and by certain bacteria to act as an extracellular signalling protein. Mycobacterium tuberculosis produces two Cpn60 proteins: Cpn60.1 and Cpn60.2. We recently generated a M. tuberculosis mutant with an inactivated cpn60.1 gene and demonstrated that granuloma formation was impaired after murine/guinea pig infection.  This finding suggested that Cpn60.1 may interact with the cellular organisation of the host response to M. tuberculosis bacilli.  In this study, we report that recombinant M. tuberculosis Cpn60.1 has both pro- and anti-inflammatory effects on human circulating monocytes. At high concentrations, recombinant Cpn60.1 induces the synthesis of TNF-α, IL6, and IL8, and promotes the phosphorylation of NF-κBp65, p44/42MAPK and p38 MAPK. At lower concentrations M. tuberculosis Cpn60.1 inhibits lipopolysaccharide-induced release of TNF-α, and monocyte transcriptional activation program. Both effects are abrogated by proteolysis of Cpn60.1 and therefore cannot be attributed to contamination with lipopolysaccharide. Competition with LPS for binding to a common receptor, the release of IL-10 or down-regulation of TLR4 on the cell surface were excluded as explanations for the inhibitory activity of Cpn60.1. We therefore conclude that M. tuberculosis Cpn60.1 is an unusual protein with the ability to induce bipolar effects on human monocytes, which may help explain the pathology of granuloma formation in tuberculosis.
We used microarrays to analyse the bipolar effectsof Cpn60.1  on human monocytes.

overall_design: To study the pro-inflammatory activities of Cpn60.1, human monocytes were purified from three healthy donors and incubated with 10 μg/ml M. tuberculosis Cpn60.1 (or 100 ng/ml LPS as a positive control or medium only as a negative control). To study the inhibitory effectds of Cpn60.1 on human monocytes, the cells were pre-exposed to 10μg/ml or 0.1ng/ml of Cpn60.1, washed and incubated with 1ng/ml LPS for further 2 hours. For positive control, the cells were pre-exposed to medium before washing and LPS stimulation while for the negative control, the cells were pre-exposed to medium, washed and again exposed to medium alone.

first: Brian

last: Henderson

first: Anthony

middle: R

last: Coates

first: Simon

middle: J

last: Waddell


title: Effect of DBC1/CCAR2 depletion on global gene expression in MDA-MB-231 cells

city: Seoul

first: Jeong

middle: Hoon

last: Kim

address: Irwon-dong Gangnam-gu

country: South Korea

institute: Sungkyunkwan University

summary:
Deleted in breast cancer (DBC1; also known as CCAR2) is a coactivator for nuclear receptors (NRs) as well as a negative regulator of epigenetic modifiers such as deacetylases SIRT1 and HDAC3.
We performed genome-wide gene expression analysis in control (shNS) and DBC1-depleted (shDBC1) MDA-MD-231 cells to investigate global gene expression changes induced by depletion of DBC1

overall_design: Total RNAs were isolated from MDA-MB-231 cells expressing shNS or shDBC1 using the RNeasy mini kit (Qiagen). The integrity of RNA was analyzed using an Agilent 2100 Bioanalyzer. Two independent biological replicates were assayed for each sample. The microarrays were performed following the Affymetrix standard protocol.

first: Hwa


title: Expression data from asthmatic and healthy  airway smooth muscle cells

city: Sydney

first: Alen

last: Faiz

state: NSW

address: 431 Glebe Point Rd

country: Australia

institute: Woolcock Institute of Medical Research

summary:
Persistent severe asthma is associated with hyper-contractile airways and structural changes in the airway wall, including an increased airway smooth muscle (ASM) mass. This study used gene expression profiles from asthmatic and healthy airway smooth muscle cells grown in culture to identify novel receptors and pathways that potentially contributed to asthma pathogenesis.
We used microarrays to compare the gene expression between asthmatic and healthy airway smooth muscle cells to understand the underlying pathway contributing the differences in cellular phenotypes

overall_design: Asthmatic airway smooth muscle cells (ASMC) are intrinsically different and have a differential transcriptional response to pro-fibrotic, pro-proliferation and pro-inflammatory stimuli than ASMC from healthy patients. We sought to identify genes that are differentially expressed between asthmatic and healthy ASMC under various stimulations which mimic the asthmatic airways. To this end, we obtained human ASMC from bronchial biopsies and explanted lungs from doctor diagnosed asthmatic patients (n=3) and healthy controls (n=3). The ASMC were then grown in culture and treated with pro-fibrotic (Transforming growth factor beta (TGFβ)), pro-proliferation (Fetal Bovine Serum (FBS)) and pro-inflammatory stimuli (Interleukin-1 beta (IL-1β)) for 8 hours. Gene expression was then evaluated using Affymetrix Human Gene 1.0ST arrays.

last: Oliver

first: Judith

last: Black

first: Janette

middle: K

last: Burgess


title: Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease.

status: Public on Jan 27 2015

city: Toronto

first: Boyko

last: Kabakchiev

state: Ontario

address: 60 Murray Street, Room L3-004

department: Samuel Lunenfeld Research Institute

institute: Mount Sinai Hospital

summary: Pouchitis is a common complication for ulcerative colitis (UC) patients with ileal pouch-anal anastomosis (IPAA) surgery. Similarly to IBD, both innate host factors such as genetics, and environmental stimuli including the tissue-associated microbiome have been implicated in the pathogenesis. In this study, we make use of the IPAA model of inflammatory bowel disease (IBD) to carry out a study associating mucosal host gene expression with the microbiome and corresponding clinical outcomes.

overall_design: In order to determine how host gene expression might influence, or be influenced by the tissue associated microbiome, we analyzed 205 IPAA patients with biopsies collected from the pouch and afferent limb for host transcriptomics and 16S rDNA gene sequencing. Metadata included antibiotic use, inflammation score, and clinical classification. To achieve power for a genome-wide microbiome-transcriptome association study, we used principal component analysis to reduce OTUs and host transcripts to eigengenes and eigenclades explaining 50% of observed variance. These were subsequently tested for significant covariation with one another and/or outcome using multivariate linear modeling.

first: B

first: X

last: Morgan

first: L

last: Waldron

first: A

last: Tyler

first: D

last: Gevers

first: R

last: Xavier

middle: S

last: Silverberg

first: C

last: Huttenhower


title: RDC and cisplatin transcriptomes

status: Public on Mar 05 2015

city: Strasbourg

first: Christian

last: Gaiddon

address: 3 av. Moliere

country: France

institute: INSERM

summary:
Ruthenium based compound have developed for anticancer therapy
Identification of the transcriptomes induced by either cisplatin or a ruthenium-based compound (RDC) that are both cytotoxic. Cells were treated with either cisplatin or RDC at their IC50 and for 6h or 24h.

overall_design: 15 samples are in the experiment. Each condition has been done in triplicates. Ct is control; R6 is RDC applied for 6h, R24 is RDC applied for 24h, C6 is ciplatin applied 6h and C24 is cisplatin applied for 24h. U87 cells were used.

last: Meng


title: Gene expression profiling in a VRK1 R358X homozygote patient

first: Sharon

last: Zeligson

summary: VRK1 mutations in humans cause a severe neuronal phenotype includung spinal muscular atrophy (SMA) and microcephaly. To study the effect of VRK1 R358X mutation on global gene expression in a homozygote human patient, an expression array was performed using EBV-trasformed B cells from the patient and two healthy controls

overall_design: Gene expression was measured in EBV-transformed B cells from from a VRK1 R358X homozygote and two healthy controls.

first: Paul

last: Renbaum

first: Ephrat

last: Levy-Lahad

first: Hadar

last: Vinograd-Byk


title: Small ncRNA expression-profiling of blood from Hemophilia A patients identifies miR-1246 as a potential regulator of Factor 8 gene

city: Bangkok

first: Tewarit

last: Sarachana

address: 154 Rama I Rd. Chulapat I Bldg. Room 1312 Wangmai Pathumwan

department: Clinical Chemistry

country: Thailand

institute: Chulalongkorn University

summary: Hemophilia A (HA) is a bleeding disorder caused by deficiency of functional plasma clotting factor VIII (FVIII). In addition to genetic mutations in the gene encoding FVIII (F8), there is evidence that other molecular mechanisms may be involved in the pathobiology of HA. In this study, global small ncRNA expression profiling analysis of whole blood from HA patients, and controls, was performed using high-throughput ncRNA microarrays. Patients were further sub-divided into those that developed neutralizing-anti-FVIII antibodies (inhibitors) and those that did not. Selected differentially expressed ncRNAs were validated by quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) analysis. We identified several ncRNAs, and among them, hsa-miR-1246 was significantly up-regulated in HA patients. In addition, miR-1246 showed a six-fold higher expression in HA patients without inhibitors. We have identified an miR-1246 target site in the noncoding region of F8 mRNA and were able to confirm the suppressory role of hsa-miR-1246 on F8 expression in a stable lymphoblastoid cell line expressing FVIII. These findings suggest several testable hypotheses vis-à-vis the role of nc-RNAs in the regulation of F8 expression and the development of anti-drug antibodies to FVIII infusions used to treat HA.

overall_design: Whole blood samples from nine patients with hemophilia A and five controls were obtained. Among those patients with hemophilia A, three of them were patients who developed neutralizing-anti-FVIII antibodies (inhibitors) and the others are patients without FVIII inhibitors. RNA was isolated and purified from all samples using the RiboPure Blood Kit (Life Technologies) according to the manufacturer’s protocol with modifications to enhance the enrichment of low molecular weight RNAs. All RNA samples were poly (A)-tailed and biotin-labeled using the FlashTag Biotin HSR RNA Labeling Kit (Affymetrix, Santa Clara, CA, USA). After labeling, the enzyme linked oligosorbent assays (ELOSA) were performed to confirm that the biotin labeling processes were successful. Biotin-labeled RNA samples (500 ng/sample) were hybridized on GeneChip miRNA 3.0 microarrays (Affymetrix). Microarray data were analyzed to identify ncRNAs that were differentially expressed in hemophilia A groups compared to controls.

first: Neetu

last: Dahiya

first: Vijaya

last: Simhadri

first: Gouri

last: Pandey

first: Surbhi

last: Saini

first: Christine

last: Guelcher

first: Michael

middle: F

last: Guerrera

first: Chava

last: Kimchi-Sarfaty

first: Zuben

last: Sauna

first: Chintamani

last: Atreya


title: Cellular and molecular characterization of the altered metabolism in RCC

status: Public on Jan 22 2015

city: Halle (Saale)

first: Anja

last: Harder

address: Große Steinstr. 52

department: Cure NF Research Group

institute: Martin Luther University Halle-Wittenberg

summary:
RCC cells (786-O) were transfected with VHL. The parental cell line should be compared to the transfectant (+ VHL) under nomoxia as well as under hypoxia conditions.
We want to distinct the VHL-mediated gene expression from the hypoxia-mediated and study the influence of both on the cellular metabolism.

overall_design: RNA of VHL-negative 786-O RCC cell line and VHL-transfectants incubated during normoxia and hypoxia conditions were analysed by cDNA microarray.

first: Ena

last: Wang

first: Sandra

last: Leisz


title: Transcriptome profiling of trisomy 21 and euploid iPSC-derived hematopoietic progenitors expressing wtGATA1 or an amino-truncated isoform of GATA1, GATA1short (GATA1s).

status: Public on Jan 26 2015

city: University Park

first: Ross

last: Hardison

state: PA

address: 303 Wartik Lab

institute: Pennsylvania State University

summary: We generated human induced pluripotent stem cells (iPSCs) from trisomy 21 (T21) and euploid patient tissues with and without GATA1 mutations causing exclusive expression of truncated GATA1, termed GATA1short (GATA1s). Transcriptome analysis comparing expression levels of genes in GATA1s vs. wtGATA1-expressing progenitors demonstrated that GATA1s impairs erythropoiesis and enhances megakaryopoiesis and myelopoiesis in both T21 and euploid contexts in the iPSC-model system.

overall_design: We analyzed the transcriptome of (i) T21 iPSC-derived heamtopoietic progenitors expressing wtGATA1 (6 replicates) or GATA1s (3 replicates), as well as of (ii) euploid iPSC-derived progenitors expressing wtGATA1 (2 replicates) or GATA1s (2 replicates).

first: Marta

last: Byrska-Bishop

first: Daniel

last: VanDorn

first: Amy

last: Campbell

first: Marisol

last: Betensky

first: Philip

middle: M

last: Arca

first: Yu

last: Yao

last: Gadue

first: Fernando

last: Costa

first: Richard

last: Nemiroff

first: Gerd

middle: A

last: Blobel

first: Deborah

last: French

first: Mitchell

last: Weiss

first: Stella

last: Chou


title: Expression data from MDA-MB-231 derived tumors grown in NOD/SCID mice: control- and Memo1-targeted shRNA pools

status: Public on Jan 23 2015

first: Tim

last: Roloff

summary: 0.5 x10^6 MDA-MB-231 cells, infected with lentivirus encoding either a control shRNA (shLacZ) or a shRNA targeting human Memo1, were injected into the second mammary fatpad of 6-8 week old female NOD/SCID mice and collected 4 weeks after injection.

overall_design: This expression data represents mRNA collected from 3 shLacZ control and 3 shMemo tumors

first: Gwen

last: MacDonald

first: Nancy

last: Hynes

first: Stephane

last: Thiry


title: Lentiviral vector-based insertional mutagenesis identifies new clinically relevant candidate cancer genes involved in the pathogenesis of hepatocellular carcinoma

city: Milan

first: Marco

last: Ranzani

address: via olgettina 58

department: TIGET

country: Italy

institute: HSR-TIGET

summary: We devised a novel insertional mutagenesis approach based on lentiviral vectors to induce hepatocellular carcinoma in three mouse models and identified four novel cancer initiating genes. Two genes are the well characterized Braf and Sos1, while the other two are Fign, encoding an AAA ATPase whose functions are poorly understood, and the paternally expressed gene Rtl1 within the complex Dlk1-Dio3 imprinted region recently involved in stemness. Interestingly, Fign and Braf regulate the expression of the maternal genes of the Dlk1-Dio3 imprinted region, suggesting that both maternally and paternally expressed genes of this region play a role in hepatocarcinogenesis. Moreover, all the genes identified are upregulated and/or amplified/deleted in human hepatocellular carcinoma and play a relevant role in human hepatocarcinogenesis, as their expression levels and/or transcriptional signatures induced by their deregulation predict a different clinical outcome in hepatocellular carcinoma patients.

overall_design: Primary human hepatocytes were transduced with SINLV.ET.trBRAF, SINLV.PGK.GFP or mock treated. RNA was collected at 5 different timepoints post-transduction: 24h, 36h, 48h, 72h, 144h (6d). Each experimental point was done in triplicate (A,B,C)

first: Daniela

last: Cesana

first: Cynthia

last: Bartholomä

first: Francesca

last: Sanvito

first: Mauro

last: Pala

first: Fabrizio

last: Benedicenti

first: Michela

last: Riba

first: Pierangela

last: Gallina

first: Lucia

last: Sergi

first: Stefania

last: Merella

first: Alessandro

last: Bulfone

first: Claudio

last: Doglioni

first: Elia

last: Stupka

first: Christof

last: Von Kalle

first: Yoon

last: Kim

first: Manfred

last: Schmidt

first: Giovanni

last: Tonon

first: Luigi

last: Naldini

first: Eugenio

last: Montini


title: Towards a reference human platelet transcriptome: evaluation of inter-individual correlations and of its relationship with a platelet proteome

status: Public on Jan 20 2015

city: Philadelphia

first: Leonard

middle: C.

last: Edelstein

address: 1015 Walnut St.

department: Medicine/Hematology

institute: Thomas Jefferson University

summary:
For the anucleate platelet it has been unclear how well platelet transcriptomes correlate among  different  donors  or  across  different  RNA  profiling  platforms,  and  what  the transcriptomes’  relationship  is  with  the  platelet  proteome.  We  generated  RNA-seq  pro-files  of  the  long  RNA  transcriptomes  from  the  platelets  of  10  healthy  young  males  (5 white and 5 black) with median age of 24.5 years, no notable clinical history, and no pre-vious history of thrombosis or bleeding. We also profiled the subjects’ messenger RNAs using the Affymetrix microarray gene expression system. We found that the abundance of  platelet  mRNA  transcripts  was  highly  correlated  across  the  10  individuals,  inde-pendently of race and of the employed technology. Our RNA-seq data also showed that these  high  inter-individual  correlations  extend  beyond  mRNAs  to  several  categories  of non-coding RNAs. Pseudogenes represented a notable exception to this by exhibiting a clear difference in expression by race. Comparison of our mRNA signatures with the only publicly available quantitative platelet proteome data showed that most (87.5%) identified platelet  proteins  had  a  detectable  corresponding  mRNA.  However,  a  high  number  of mRNAs that were present in the transcriptomes of all 10 individuals had no representa-tion  in  the  proteome.  The  Spearman  correlation  of  the  relative  abundances  for  those platelet  genes  that  were  represented  by  both  an  mRNA  and  a  protein  showed  a  weak (~0.3) yet statistically significant (P=5.0E-16) connection. Further analysis of the overlap-ping  and  non-overlapping  platelet  mRNAs  and  proteins  identified  gene  groups  corre-sponding to distinct cellular processes, a finding that provides novel insights for platelet biology.
This represents the Affymetrix GeneChip component of the study only

overall_design: 10 Resting Human Platelet samples

first: Paul

last: Bray

first: Isidore

last: Rigoutsos


title: Expression data from chimeric antigen receptor transduced (CAR) human CD4+ T cells during expansion

status: Public on Jan 14 2015

first: Carl

last: June

state: Pennsylvania

address: 3400 civic center blvd STRC 421 8-123

department: Department of Pathology

institute: University of Pennsylvania

summary: In this data set we include expression data from human CD4+ T cells isolated on day 0, 6, 11 and 24 follow anti-CD3/anti-CD28 magnetic bead stimulation and chimeric antigen receptor transduction.

overall_design: 30 samples were submitted. Samples represented three biological replicates of normal donors transduced with various CARs. CARs used were a cMet 28z specific CAR comprised of the IgG4 hinge, CD28 transmembrane and CD28 and CD3zeta intracellular domains. A CD19 CD28 CAR was specific to CD19, and was comprised of a CD8a hinge, CD28 transmembrane and CD28 and CD3zeta intracellular domain. A third CAR, the CD19 BBz, was used that was specific to CD19 was comprised of a CD8a hinge, CD8a transmembrane and 4-1BB and CD3zeta intracellular domains. Expression data was analyzied on day 0, 6, 11 and 24.

middle: H

first: Matthew

last: Frigault


title: Molecular regulation of acute kidney injury (miRNA)

status: Public on Jan 15 2015

city: Vienna

first: Julia

last: Wilflingseder

address: Währinger Gürtel 18-20

department: Nephrology and Dialysis

country: Austria

institute: Medical University of Vienna

summary: 18 zero-hour and 18 selected post-transplant (Tx) biopsy samples from 18 kidney allografts (8 acute kidney injury (AKI), 10 PBx - protocol biopsies - controls) were analyzed by using the Affymetrix GeneChip® miRNA 3.0 Array.

overall_design: Comparison between control group (protocol biopsies) and indication biopsies with histological lesions of acute tubular necrosis without rejection (ATN).

first: Rainer

last: Oberbauer


title: Comparison of human aortic valve interstitial cells (AVICs) exposed to cyclic stretch to static samples

status: Public on Jan 09 2015

city: Seattle

first: Vishal

last: Nigam

state: WA

address: 1900 9th Ave

department: Pediatrics

institute: Seattle Childrens Research Institute

summary:
AVICs were exposed to cyclic stretch to examine the role of mechanical stimuli on gene expression
AVICs cultured on collagen 1 coated Bioflex were exposed to 14% stretch at 1 hz or static conditions using a Flexcell-5000

overall_design: 14% stretch was the experimental condition while the static condition was the control

first: V


title: Expression data from H295R_GRα cells following treatment with dexamethasone or RU486

status: Public on Jan 10 2015

first: Roderick

last: Clifton-Bligh

address: Westbourne St St Leonards

department: Cancer Genetics

institute: Kolling Institute of Medical Research, University of Sydney

summary:
The human glucocorticoid receptor (GRα) is overexpressed at the molecular and protein level in malignant human adrenocortical cancers. A stable cell line model of GRα overexpression was established using the H295R human adrenocortical cancer cell line.
The following results were obtained from gene expression profiling of H295R_GRα and H295R_Control (empty vector) cells following treatment with either a GRα agonist (dexamethasone), GRα antagonist (RU486) or vehicle (ethanol) control.

overall_design: H295R_GRα and H295R_Control (empty vector) cells were treated in triplicate for 6 hours with dexamethasone 100 nM, RU486 100 nM or vehicle (ethanol) control.

first: Lyndal

last: Tacon


title: CD14 and complement crosstalk and largely mediate the transcriptional response to Escherichia coli in human whole blood as revealed by DNA microarray

status: Public on Jan 08 2015

city: Bodø

first: Corinna

last: Lau

address: Prinsensgate 164

department: Research Department

country: Norway

institute: Nordland Hospital Bodø

summary: Systemic inflammation like in sepsis is still lacking specific diagnostic markers and effective therapeutics. The first line of defense against intruding pathogens and endogenous damage signals is pattern recognition by e.g., complement and Toll-like receptors (TLR). Combined inhibition of a key complement component (C3 and C5) and TLR-co-receptor CD14 has been shown to attenuate certain systemic inflammatory responses. Using DNA microarray and gene annotation analyses, we aimed to decipher the effect of combined inhibition of C3 and CD14 on the transcriptional response to bacterial challenge in human whole blood. Importantly, combined inhibition reversed the transcriptional changes of 70% of the 2335 genes which significantly responded to heat-inactivated Escherichia coli by on average 80%. Single inhibition was less efficient (p<0.001) but revealed a suppressive effect of C3 on 21% of the responding genes which was partially counteracted by CD14. Furthermore, CD14 dependency of the Escherichia coli-induced response was increased in C5-deficient compared to C5-sufficient blood. The observed crucial distinct and synergistic roles for complement and CD14 on the transcriptional level correspond to their broad impact on the inflammatory response in human blood, and their combined inhibition may become inevitable in the early treatment of acute systemic inflammation.

overall_design: A microarray study was performed on whole blood from two healthy donors, a C5-deficient patient (C5D) (with and without C5-reconstitution) incubated for 120 min at 37oC with (i) PBS, (ii) E. coli or (iii) E. coli and inhibitors of complement (C3 or C5aR) and/or CD14 or inhibitor controls. The experiments were performed as biological replicates on two different days (healthy donor and C5D). Due to lack of a second C5-deficient patient, microarray analyses were prerformed twice (technical replicate) for C5D and day 1. Expression data in presence of PBS were used as reference for those in pressence of E. coli. Expression data in presence of E. coli were used as reference for those in pressence of E. coli and inhibitors. Expression data from 0 min incubation with PBS represent the initial state (T0). Whole blood was lysed in Applied Biosystems AB6100 total RNA chemistry lysis buffer and stored at -80oC prior to RNA extraction.

first: Ole

last: Olstad

first: Marit

last: Holden

first: Ståle

last: Nygård

first: Hilde

last: Fure


title: Whole-blood transcriptomic profiling highlights rituximab response in rheumatoid arthritis

status: Public on Jan 01 2015

city: 91400 Orsay

first: Florent

last: Dumont

state: Ile de France

address: 17 avenue des sciences

institute: Université Paris-Saclay

summary: Objective: We performed whole-blood transcriptomic profiling for patients with rheumatoid arthritis (RA) who received rituximab (RTX). We aimed to identify a molecular signature that could predict the clinical response to RTX and transcriptomic changes after RTX therapy.

overall_design: Methods: We performed a microarray assay of the whole human genome with RNA from a peripheral blood sample taken before the first RTX cycle from 68 patients included in the SMART study (24 EULAR non-responders and 44 responders at week 24). The transcriptomic profile was also assessed 24 weeks after the first RTX administration

first: J

last: Sellam

first: S

last: Marion-Thore

first: F

last: Jacques

first: H-J

last: Garchon

last: Rouanet

first: Y

last: Taoufik

first: H

last: Chavez

last: Sibilia

last: Tebib

first: X

last: Loët

first: B

last: Combe

first: M

last: Dougados

last: Mariette

first: G

last: Chiocchia


title: Affymetrix SNP array data of melanoma cell lines

city: Essen

first: Klaus

middle: Georg

last: Griewank

address: Hufelandstr. 55

department: Dermatology

institute: University of Duisburg-Essen

type: Genome variation profiling by genome tiling array

summary: B2M losses are seen as an early event, shared by all cell lines presented here

overall_design:
Cell lines were generated from tumor material, differences in T cell recognition were observed and Affymetrix SNP arrays were performed according to the manufacturer's instructions on DNA extracted from cell lines
SNP analysis of different melanoma cell lines obtained from 2 melanoma patients (3 cell lines from different metastases of one patient with matching germline DNA and 2 cellines from metastases of another patient) show alterations of the B2M gene

first: Annette

last: Paschen


title: Mucosal gene expression profiling in (un)inflamed colon of patients with ulcerative colitis (UC)

city: Leuven

first: Jan

last: Van der Goten

address: Herestraat 49 bus 701

department: Clinical and Experimental Medicine

country: Belgium

institute: KU Leuven

summary: In this study, we investigated if miRNA expression in UC mucosa is altered and correlated our findings with mucosal mRNA expression. Integration of mRNA and miRNA expression profiling may allow the identification of functional links between dysregulated miRNAs and their predicted target mRNA.

overall_design: Colonic mucosal biopsies were obtained during endoscopy from 13 UC (7 active and 6 inactive) patients and 8 normal controls. Total RNA was isolated from colonic mucosal biopsies, labelled and hybridized to Affymetrix Genechip Human Gene 1.0ST Arrays.

first: Leentje

last: Van Lommel

first: Marc

last: Ferrante

first: Gert

last: Van Assche

first: Paul

last: Rutgeerts

first: Frans

last: Schuit

first: Séverine

last: Vermeire

first: Ingrid

last: Arijs


title: Mucosal expression profiling in (un)inflamed colon of patients with ulcerative colitis (UC)

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

overall_design: Refer to individual Series


title: Transcription Profiling of MDA-MB231 breast cancer cells overexpressing the GHSROS gene

city: Kelvin Grove

first: Inge

last: Seim

state: Queensland

address: 60 Musk Avenue

institute: Queensland University of Technology

summary: The purpose of this experiment was to compare the gene expression pattern of stable, polyclonal cells overexpressing the candidate non-coding gene GHSROS to vector-only (empty pTargeT vector) cells.

overall_design: Three biological replicates of MDA-MB231 cells transfected with the gene GHSROS or empty vector.


title: miRNA data in colon mucosa samples from individuals with ulcerative colitis and normal controls

city: Houston

first: R.

middle: Alan

last: Harris

state: TX

address: 1 Baylor Plaza

department: Molecular and Human Genetics

country: USA

institute: Baylor College of Medicine

summary: Genome wide miRNA profiling of ulcerative colitis, and normal colon mucosa samples. The GeneChip miRNA 3.0 Array was used to obtain miRNA profiles across colon mucosa samples. Samples came from 5 ulcerative colitis affected, and 5 normal individuals.

overall_design: miRNA from the 10 samples were hybridized to the GeneChip miRNA 3.0 Array

first: Richard

last: Kellermayer

first: R


title: Effect of ZFX shRNA mediated knockdown in the human AML cell line NOMO-1

city: New York

first: Stuart

last: Weisberg

state: NY

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: NOMO-1 cells were infected with control and ZFX shRNA lentiviruses at an MOI of 1. RNA was collected for microarrays 48 hours after selection.

middle: P

first: Boris

middle: V

last: Reizis


title: Bone marrows from neuroblastoma patients: an excellent source for tumor genome analyses

status: Public on Dec 31 2014

first: Peter. F.

last: Ambros

address: Zimmermannplatz 10

department: Tumor Biology

institute: Children's Cancer Research Institute

summary: Neuroblastoma is the most common extra-cranial solid tumor in childhood. Presence of disseminated tumor cells (DTCs) in the bone marrow (BM) at diagnosis and at relapse is a common event in stage M neuroblastomas. Although the clinical heterogeneity of disseminated neuroblastomas is frequently associated with genomic diversity, so far, only little information exists about the genomic status of DTCs. This lack of knowledge is mainly due to the varying amount of BM infiltrating tumor cells, which is usually below 30% even at diagnosis thereby hampering systematic analyses. Thus, a valuable chance to analyze metastatic and relapse clones is, so far, completely unexploited.  In this study, we show that the enrichment of tumor cells in fresh or DMSO frozen BM samples with a minimum of 0.05% or 0.1% infiltration rate, respectively, by applying magnetic beads technique increased the DTC content to a sufficient level to allow SNP array analyses in 49 out of 69 samples. In addition, we successfully used non-enriched BM samples with ≥30% DTCs including non-stained and immunostained cytospin and BM smear slides for SNP array analyses in 44 cases.  We analyzed the genomic profile of DTCs by an ultra-high density SNP array technique with highest performance detecting all segmental chromosomal aberrations, amplified regions, acquired loss of heterozygosity events and minor aberrations affecting single genes or parts thereof.

overall_design: Affymetrix CytoScan HD arrays were performed according to the manufacturer's directions on DNA extracted from disseminated tumor cells in the bone marrow or tumor samples.

first: M

last: Abbasi

first: Fikret

last: Rifatbegovic

first: Clemens

last: Brunner

first: Ruth

last: Ladenstein

first: Peter


title: Analysis of Gene Expression and Cytokine Release Profiles Reveals the Inter-depot and Intra-depot Genetic and Functional Heterogeneity of Human Adipose Tissue-Derived Stem Cells

city: Bari

first: Ernesto

last: Picardi

address: Via Orabona

institute: University of Bari

summary: Differences in the inherent properties of undifferentiated fat cell progenitors may contribute to the biological specificity of the abdominal subcutaneous (Sc) and visceral omental (V) fat depots. In this study, the biological characteristics of three distinct subpopulations of adipose tissue-derived stem cells (ASC), i.e. ASCSVF, ASCBottom and ASCCeiling isolated from Sc and V adipose tissue biopsies of non-obese subjects, were investigated. Genome-wide differential gene expression analysis followed by quantitative RT-PCR and analysis of cytokines in the ASC-derived conditioned medium were performed. By analysis of 28,869 annotated genes, 1,019 genes resulted differentially expressed between Sc-ASC and V-ASC. Within the Sc-ASC and V-ASC populations, 546 and 1,222, respectively, were the genes differentially expressed among ASCSVF, ASCBottom and ASCCeiling. A far more striking difference was found when the hierarchical clusters analysis was performed comparing each Sc-ASC with its own homologous V-ASC subset. mRNA levels of HoxA5, Tbx15, PI16, PITPNC1, FABP5, IL-6, IL-8, MCP-1, VEGF, MMP3, TFPI2, and ANXA10 were significantly different between Sc-ASC and V-ASC. Of the 27 cytokines measured, 14 (IL-2, IL-4, IL-5 IL-7, IL-9, IL-10, IL12, IL13, MIP1-α, MIP1-β, PDGF-ΒΒ, FGFbasic, GM-CSF, IP-10) were not released, whereas 13 were expressed (IL-1beta, IL-1ra, IL-15, IL-17, G-CSF, IFNγ, RANTES, TNF-α, Eotaxin, IL-8, MCP-1, VEGF, IL-6), and of these, MCP-1, Eotaxin, IL-1ra, FGFbasic, IL-6, IL-8, G-CSF, and VEGF were significantly different among ASCSVF, ASCCeiling and ASCBottom of the two adipose tissue depots. These results demonstrate the existence of genetically and functionally heterogeneous fat-derived ASC populations, which may add to the complexity and specificity of Sc and V adipose tissue in humans.

overall_design: Total RNA was isolated from the ASC of 5 lean subjects. The quality and integrity of total RNA (RNA Integrity Number [RIN] ≥8.0) was evaluated on an Agilent Bioanalyzer (Agilent Technologies, Waldbronn, Germany). RNA was then processed for hybridization on Human Gene 1.0 ST Array chips (Affymetrix, High Wycombe, UK), covering 28,869 well-annotated genes with 764,885 distinct probes, using standard Affymetrix protocols.

first: Sebastio

last: Perrini

first: Romina

last: Ficarella

first: Angelo

last: Cignarelli

first: Maria

last: Barbaro

first: Pasquale

last: Nigro

first: Alessandro

last: Peschechera

first: Orazio

last: Palumbo

first: Massimo

last: Carella

first: Michele

last: De Fazio

first: Annalisa

last: Natalicchio

first: Luigi

last: Laviola

first: Graziano

last: Pesole

first: Francesco

last: Giorgino


title: METRONOMIC TOPOTECAN CAUSES THERAPY-INDUCED TUMOR CELL SENESCENCE AND LOSS OF AGGRESSIVE PROPERTIES IN MYCN-AMPLIFIED CHILDHOOD CANCER [Affymetrix Cytoscan HD]

first: Maximilian

last: Kauer

department: Molecular Biology

institute: CCRI, St.Anna Children Cancer Research Institute

summary: Evidence is accumulating that senescence drives cure in various murine and human malignancies. We demonstrate that metronomic, repetitive low-dose topotecan treatment leads to tumor cell senescence in vitro and in vivo and long-term cure in a model for the aggressive childhood cancer neuroblastoma. By using the senescence-associated secretory phenotype (SASP) as a discriminator for beneficial versus adverse effects of senescence, we identified topotecan as inducer of a favorable SASP. Senescent tumor cells are growth arrested and act growth inhibitory on co-cultured non-senescent tumor cells. MYCN oncogene amplification and expression, hallmarks of aggressive neuroblastoma, are significantly reduced, supporting an initial transition to a more favorable phenotype. These new aspects of metronomic drug treatment are clinically relevant and might apply to other tumor entities.

overall_design: In total, 4 samples were analysed by Affymetrix Cytoscan HD array for copy number and SNP: two different neuroblastoma cell lines, STA-NB-10 and CLB-Ma, control and 3 or 5 nM Camptothecin (3-weeks long-term)

first: Sabine

last: Taschner-Mandl

first: Magdalena

last: Schwarz

first: Johanna

last: Blaha

first: Martin

last: Hohenegger

first: Florian

last: Kromp

first: Nelli

last: Frank

first: Fikret

last: Rifatbegovic

first: Inge

last: Ambros


title: In vitro gene expression profile of TGFbeta-regulated genes in MCF10A-based xenograft model of breast cancer progression

city: Bethesda

first: Howard

last: Yang

state: MD

address: 37 CONVENT DR, Room 5120

department: CCR

institute: NCI

summary:
TGF-betas have complex roles in tumorigenesis, with context-dependent effects that can either suppress or promote tumor progression. Our goal was to use integrated genomic approaches in a model of human breast cancer progression to identify core TGF-beta-regulated genes that specifically reflect the tumor suppressor activity of TGF-beta. The model consisted of the non-tumorigenic MCF10A (“M1”), the premalignant MCF10AT1k.cl2 (“M2”), the early malignant MCF10Ca1h (“M3”) and the highly malignant, metastatic MCF10Ca1a.cl1 (“M4”) cell lines.  We have previously shown that tumor suppressor activity of TGF-beta is lost in the highly malignant M4 cells.
To determine how the spectrum of TGF-beta-regulated genes changes with cancer progression, we performed gene expression array analysis on  four cell lines of the MCF10A-based model of breast cancer progression (M1-M4) cultured in vitro under serum-free conditions and treated with TGF-beta (5ng/ml plus condition) or vehicle (minus condition) for 1h or 6h.

overall_design: The cell lines used consisted of the non-tumorigenic MCF10A (“M1”), the premalignant MCF10AT1k.cl2 (“M2”), the early malignant MCF10Ca1h (“M3”) and the highly malignant, metastatic MCF10Ca1a.cl1 (“M4”). M1-M4 cells were treated in vitro with 5ng/ml of TGF-b1 or vehicle for 1hour and 6 hour.  RNA was isolated for gene expression analysis. Three biological replicates for each condition were analyzed using the Affymetrix GeneChip Human ST1.0 array (total of 48 CEL.files).

first: Misako

last: Sato

first: Mitsutaka

last: Kadota

first: Binwu

last: Tang

first: Robert

last: Clifford

first: Aleksandra

last: Michalowski

first: Maxwell

last: Lee

first: Lalage

last: Wakefield


title: Effect of cigarette smoke extract, cisplatin, nicotine and/or ionizing radiation on gene expression in the NCI-H460 human lung large cell carcinoma cell line

city: Buffalo

first: Santosh

middle: Kumar

last: Patnaik

address: Elm and Carlton Streets

department: Thoracic Surgery

institute: Roswell Park Comprehensive Cancer Center

summary: To understand the effect of nicotine on sensitivity of cancer cells to radiation or anti-cancer drugs, NCI-H460 human lung large cell carcinoma cells were treated with 6 Gy ionizing radiation or 1 uM cisplatin after exposure to 5 uM nicotine or cigarette smoke extract. Whole genome expression in total RNA extracted from the treated cells was quantified using the GeneChip™ Human Gene 1.0 ST microarray platform from Affymetrix® (Santa Clara, CA).

overall_design: Cells were subjected to one of nine types of treatment in triplicate and harvested for RNA extraction after 2 or 24 hours. Thus, 54 RNA samples representing biological triplicates for nine types of treatments and two time-points were obtained and analyzed using microarrays (one array per RNA sample, without technical replication).

first: Michelle

last: Romano

first: Samantha

last: Sobus

first: Krista

last: Pundt

first: Sai

last: Yendamuri

first: Graham

last: Warren


title: Leukotriene D4 induces early genes in Hodgkin lymphoma cells through Cysteinyl leukotriene type I receptor

city: Stockholm

first: Yongtao

last: Xue-Franzen

address: Solnavagen 9

institute: Karolinska Insititutet

summary: Leukotriene (LT) D4 contributes to aberrant cytokine networks of classical Hodgkin lymphonoma, This study has investigated LTD4 induced gene expression and pathway in Hodgkin lymphonma cell line L1236.

overall_design: Human Hodgkin lymphoma cells are treated with Leukotriene (LT) D4 for 1 hour and 8 hour respectively, the expression profile are compared to non-treated control cells and methanol treated vihicle controls at the two time points.

first: Hongya

last: Han

last: Xue-Franzén


title: Gene expression data from whole blood of Klinefelter Syndrome patients compared to male and female controls

status: Public on Jan 07 2015

city: Muenster

first: Steffi

last: Werler

address: Albert-Schweitzer-Campus 1 (D11)

department: Center for Reproductive Medicine and Andrology

country: Germany

institute: University Hospital Muenster

summary:
Patients with Klinefelter Syndrome have the karyotype 47,XXY. These men are suffering from hypergonadotropic hypogonadism and are infertile. It is debated whether the different hormonal constitution observed in these patients or different gene expression
With the Microarray analysis we could identify genes on the X-chromosomes that are upregulated in KS-patietns compared to healthy male controls. But also autosomal genes were found to be differentially regulated.

overall_design: mRNA was isolated from whole blood of 35 KS-patients and 15 healthy male and 15 healthy female controls and hybridization on Affymetrix Arrays.


title: Effect of lentiviral-based shRNA-mediated knockdown of ZFX on the human medulloblastoma (MB) cell-line DAOY

first: Colin

last: Palmer

state: New York

address: 701 W. 168th Street

department: Microbiology & Immunology

summary: The Hedgehog (Hh) signaling pathway regulates normal development and cell proliferation, whereas its aberrant activation causes tumor formation. Hh-induced tumors can arise from different tissues and can be indolent or highly aggressive, such as basal cell carcinoma (BCC) of the skin and neural progenitor-derived medulloblastoma (MB), respectively. Little is known about cell-intrinsic factors that control the development of such diverse Hh-dependent tumors. Transcription factor Zfx is required for the self-renewal of several stem cell types, whereas its role in malignant transformation remains controversial. We found that the deletion of Zfx prevented BCC formation and significantly delayed MB development caused by Hh activation in vivo. In contrast, Zfx was dispensable for the development of Hh-independent brain tumor glioblastoma. We used genome-wide expression and chromatin binding analysis in a human MB cell line to identify direct, evolutionarily conserved targets of Zfx. These targets included the Hh signal transducer Smoothened (Smo), suggesting that Zfx may directly control Hh pathway activation in tumors. Two additional targets of Zfx, Dis3L and Ube2j1, were also required for the growth of MB cells in vitro. These results identify a common cell-intrinsic regulator of diverse Hh-induced tumors, and suggest Zfx and Zfx-controlled genes as possible therapeutic targets in these malignancies.

overall_design: DAOY cells were transduced for 16-24 hours with lentivirus encoding shRNA targeting ZFX (H2, H3, H4) or scrambled non-targeting shRNA (SCR). Cells were allowed to recover for 48 hours, and then were replated in 2 ug/mL puromycin selective media. Cells were collected in TriZol LS reagent for RNA for microarrays ~48 hours after start of puromycin selection.

first: Boris

last: Reizis


title: Expression data from MDA-MB-231 cells over-expressing RRP1B and MDA-MB-231 control cells with endogenous RRP1B levels

first: Nigel

last: Crawford

address: 50 South Drive, Room 5154

institute: Human Genome Research Institute

summary:
RRP1B is a breast cancer metastasis suppressor that interacts with various regulators of gene transcription
We examined the changes in gene expression caused by the stable over-expression of RRP1B using lentiviral transduction in the human breast cancer cell line MDA-MB-231.

overall_design: 10 total samples were analyzed. We generated the following pairwise comparisons using Partek: WT<Ctrl;. Genes with a Benjamini-Hochberg corrected p-value <0.05 and a fold-change ≥abs(2.5) were selected.

first: Minnkyong

first: Amy

last: Dworkin

first: Niraj

last: Trivedi


title: Expression data comparing HCC CSC cells and non-CSC cells

status: Public on Dec 26 2014

city: Guangzhou

first: Qiu-Zhong

last: Pan

address: 651 Dongfeng Road East

country: China

institute: Sun Yat-Sen University Cancer Center

summary: To identify novel molecular markers associated with the maintenance of HCC CSCs

overall_design: Huh7 HCC cell line was sorted into CD133+ (or ALDH+) and CD133- (or ALDH-) subpopulations by flow cytometry

first: Ke


title: Notch1 activation and TGF-beta stimulation in transformed human esophageal cells

first: Hiroshi

last: Nakagawa

address: 415 Curie Blvd.

department: Gastroenterology Division

institute: University of Pennsylvania

summary:
Transformed human esophageal keratinocyte cell line EPC2-T (EPC2-hTERT-EGFR-cyclin D1-p53R175H) cells were stimulated with or without 2.5 ng/ml recombinant human TGF-beta1 for 10 days.
The above cells were subjected to treatment for 10 days with or without 0.5 µg/ml doxycycline (DOX) to activate tetracycline-inducible (tet-on) ICN1, an active form of Notch1.

overall_design: Transformed human esophageal keratinocytes EPC2-T (EPC2-hTERT-EGFR-cyclin D1-p53R175H) were stably transduced with tetracycline-inducible ICN1 (active form of Notch1). Cells were treated for 10 days either with or without 2.5 ng/ml recombinant human TGF-beta1 (TGF) along with or without 0.5 µg/ml doxycycline (DOX). Then, cells were subjected to RNA extraction in triplicate for gene array experiments. Four conditions were compared: (1) neither TGF-beta1 treatment nor Notch1 activation (cont); (2) Notch1 activation only (DOX); (3) TGF-beta1 stimulation only (TGF); (4) Notch1 activation plus TGF-beta1 stimulation (DOXTGF).

first: Anil

last: Rustgi


title: Across-species comprehensive copy number analyses identifies subtype-specific drivers of breast cancer development

city: Chapel Hill

first: Charles

middle: M.

last: Perou

state: NC

address: 12-044 Lineberger Comprehensive Cancer Center CB# 7295

department: Professor of Genetics, and Pathology & Laboratory Medicine; Lineberger Comprehensive Cancer Center

institute: University of North Carolina at Chapel Hill

summary: A large number of DNA copy number alterations (CNAs) exist in human breast cancers, and thus characterizing the most frequent ones is key to advancing therapeutics because it is likely that these recurrent CNAs contain breast tumor ‘drivers’ (i.e. causal genes). Here, we have comprehensively profiled a large set of human breast tumors and mouse models of mammary cancers using DNA copy number and gene expression microarrays. By using an across species genetic conservation approach, we identified common altered regions/genes that were similarly altered in both human and mouse breast tumors; additionally, we further demonstrate that many of these conserved CNA regions are also expression-subtype specific, such as the common gain of 1q21-23, or loss of 5q in mouse and human Basal-like cancers. Published functional studies further validated likely driver genes from these regions including Nicastrin (NCSTN) on 1q23 in Basal-like breast cancers. The ability to integrate copy number, and expression data, from mouse and human breast tumors identified at least 25 regions of shared subtype specific alternations, which has identified a number of known drivers and a few regions that merit additional studies.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design:
This submission is comprised of: 159 Human breast tumors by aCGH (Illumina)
The complete study is comprised of: 159 Human breast samples by microarray (150 samples from primary sites, 9 from sites of metastasis);  209 Mouse mammary samples by microarray (232 mouse tumors and 10 normal mammary tissues, comprising 18 different gene constructs);  159 Human breast tumors by aCGH (Illumina);  73 Murine breast tumors by aCGH (Agilent)

first: Grace

last: Silva


title: Expression profiling by array

first: Gabriela

last: Bomfim Ferreira

state: Vlaams-Brabant

address: Herestraat 49 bus 902

summary: We used microarrays to investigate the global program of gene expression in human differentiating monocytes in the presence of the bio-active from of vitamin D.

overall_design: Human CD14+ monocytes were isolated from PBMCs of healhty donors and cultured in the presence of 1,25(OH)2D3 (10-8M) or ethanol for 4h or 24h. Total RNA was then isolated and analyzed by microarray. Four monocytic preparations from different healthy donors were used.

first: Lut

last: Overbergh

first: Chantal

last: Mathieu


title: CD44-high Cancer stem-cell like cell fraction in transformed human esophageal cells

city: Philadelphia

summary:
Comparison of CD44-high/CD24-low (CD44H) and CD44-low/CD24-high (CD44L) cell fractions in transformed human esophageal cell line EPC2-T
CD44H cells display enhanced malignant potential (e.g. tumorigenicity, colony formation) compared to CD44L cells.

overall_design: Transformed human esophageal keratinocyte cell line EPC2-T (EPC2-hTERT-EGFR-cyclin D1-p53R175H) appeared to contain two cell populations defined by high expression of CD44 (CD44H) as well as low expression of CD44 (CD44L). The former (CD44H) displayed fibroblast-like mesenchymal morphology while the latter (CD44L) remained cuboidal epithelioid morphology in culture. CD44H and CD44L cells were sorted by fluorescence-activated cell sortingand subjected to RNA extraction and gene array experiments.


title: Effect of cigarette smoke extract, cisplatin, nicotine and/or ionizing radiation on mRNA and microRNA expression in the NCI-H460 human lung large cell carcinoma cell line

first: Santosh

last: Patnaik

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

platform_organism:
Homo sapiens
Human alphaherpesvirus 1
Human alphaherpesvirus 2
Cytomegalovirus
Human betaherpesvirus 5
Lymphocryptovirus
Rhadinovirus
JC polyomavirus
Human immunodeficiency virus 1
Murid gammaherpesvirus 4
Merkel cell polyomavirus
Betapolyomavirus hominis
Betapolyomavirus macacae

overall_design: Refer to individual Series


title: Experimentally identified targets of a subset of adenovirus 5-encoded miRNAs.

status: Public on Dec 23 2014

city: Vienna

first: Maximilian

last: Kauer

summary: Human adenovirus 5 encodes a small set of miRNAs, which are generated by DICER-mediated processing of 2 larger precursors, the so-called virus-associated RNAs I and II. To identify targets of one of the major miRNA isoforms derived from virus-associated RNAI (mivaRNAI-137), we isolated Argonaute complexes of mivaRNAI-137-transfected cells and analyzed co-purifying RNAs by microarray analysis. RNAs enriched in Argonaute complexes of mivaRNAI-137-transfected cells compared to cells transfected with a control siRNA were identified and subjected to further validation. RNAs specifically associated with Argonaute-containining complexes of adenovirus 5-infected cells were identified as well.

overall_design:
9 sets of RNAs isolated from Argonaute-containing complexes of cells transfected with 2 types of adenovirus 5-encoded miRNAs or a negative control siRNA as well as the corresponding total RNA were subjected to microarray analysis.
Consequences on gene expression of hypoxic condition created by exposure of cells to 1% oxygen in a hypoxia chamber.

first: Florian

last: Bellutti

first: Kauer

last: Maximilian

first: Kneidinger

last: Doris

first: Klein

last: Reinhard


title: Hypoxic MDA-MB-231 miRNA array

city: Jupiter

first: Donald

middle: G.

last: Phinney

state: Florida

address: 130 Scripps Way Bldg A215

department: Molecular Medicine

institute: The Scripps Research Institute

summary:
MiR-544 was inhibited by either a miR-544 antagomir or compound 1 under hypoxic conditions in MDA-MB-231 cells
MiRNA microarray was utilized to examine the specificity of 1 for miR-544.

overall_design: 3 MDA-MB-231 samples treated with a miR-544 antagomir or compound 1 were subjected to hypoxia for a period of 5 days.  After 5 days, samples were pooled and subjected to miRNA microarray analysis.

first: Christopher

last: Haga


title: Expression data from whole blood samples of Rwandan adults with mild malaria with matched sample thirty days later (convalescence)

status: Public on Dec 19 2014

city: Bronx

first: Johanna

middle: Patricia

last: Daily

address: 1301 Morris Park Avenue, Price Center

department: Medicine (Infectious Disease)

institute: Albert Einstein College of Medicine

summary:
Host factors governing mild disease in adults who have developed clinical immunity to Plasmodium falciparum may provide insights for disease altering vaccine or interventions, to prevent severe malaria
We used microarrays of whole blood samples during mild malaria and compared them in a paired analysis to whole blood microarray 30 days later. (n=19 pairs)

overall_design: 3mL of whole blood was immediately placed in Tri-Reagent BD, frozen; high quality pairs were selected, were randomly selected for hybridization and analysis. Sense strand cDNA was generated from total RNA using the Ambion® WT Expression Kit (Life Technologies, Grand Island, NY) and labeling was done with the GeneChip® WT Terminal Labeling Kit (Affymetrix, Santa Clara, CA) for use with the GeneChip® Human Gene 1.0 ST Arrays (Affymetrix). The array image was generated by a high-resolution GeneArray Scanner 3000 7G (Affymetrix).

first: Krisanthi

last: Subramaniam


title: Expression data from cells overexpressing c19orf63 (HSS1) [A172]

status: Public on Dec 22 2014

city: Pasadena

first: Katiana

last: Junes-Gill

state: CA

address: 133 N Altadena Dr

institute: Neumedicines, Inc.

summary:
A172 cell lines were stable transfected with C19ORF63 (Human hematopoietic peptide secreted-1 - HSS1). HSS1 is a truly novel protein defining a new class of secreted factors.  A172 cell line overexpressing HSS1 greatly reduced their proliferation rate compared to mock-transfected cells.
Microarray analysis was used to detail gene expression underlying the anti-proliferative and anti-tumorigenic effect of HSS1 in A172 cells.

overall_design: Exponentially growing A172 cells at growth curve day 4 were harvested for total RNA extraction and hybridization on Affimetrix microarrays. Four groups of samples were evaluated in biological triplicates: A172 wild-type, A172 -pcDNA3.1 mock-transfected, A172-pcDNA-HSS1 clone#7 and  A172-pcDNA-HSS1 clone#8. Cells were stable transfected with pcDNA3.1 empty vector or hHSS1. hHSS1-expressing cells and control cells were at confluence 40-80% when harvested. Trypan blue analysis of the number of viable cells showed a significant anti-proliferative effect in A172 cells expressing hHSS1 as compared to the control cells.

first: Lena

last: Basile


title: Expression data from cells overexpressing c19orf63 (HSS1) [U87]

summary:
U87 cell lines were stable transfected with C19ORF63 (Human hematopoietic peptide secreted-1 - HSS1). HSS1 is a truly novel protein defining a new class of secreted factors.  U87 cell line overexpressing HSS1 greatly reduced their proliferation rate compared to mock-transfected cells.
Microarray analysis was used to detail gene expression underlying the anti-proliferative and anti-tumorigenic effect of HSS1 in U87 cells.

overall_design: Exponentially growing U87 cells at growth curve day 5 were harvested for total RNA extraction and hybridization on Affimetrix microarrays. Three groups of samples were evaluated in triplicates: U87 wild-type, U87 -pcDNA3.1 mock-transfected, U87-pcDNA-HSS1. Cells were stable transfected with pcDNA3.1 empty vector or hHSS1. hHSS1-expressing cells and control cells were at confluence 40-80% when harvested. Trypan blue analysis of the number of viable cells showed a significant anti-proliferative effect in U87 cells expressing hHSS1 as compared to the control cells.


title: CD24-low Cancer stem-cell like cell fraction in Notch inhibited transformed human esophageal cells

first: Hiroshi

last: Nakagawa

summary: Comparison of CD24-low/CD44-high (CD44H) and CD24-high/CD44-low (CD44L) cell fractions in transformed human esophageal cells with Notch inhibition. CD44H cells display enhanced malignant potential (e.g. tumorigenicity, colony formation) compared to CD44L cells.

overall_design: NOTCH signaling was suppressed by retrovirus-mediated stable transduction of dominant-negative Mastermind-like1 (DNMAML1) in transformed human esophageal keratinocyte cell line EPC2-T (EPC2-hTERT-EGFR-cyclin D1-p53R175H) as described (Gastroenterology. 2010;139:2113-23), resulting in creation of cell line designated 4801. 4801 cells were sorted by flow cytometry for a cell fraction expressing a low level of CD24 and a high level of CD44 (CD44H) as well as that expressing a high level of CD24 and a low level of CD44 (CD44L). The former (CD44H) displayed fibroblast-like mesenchymal morphology while the latter (CD44L) remained cuboidal epithelioid morphology in culture. CD24-low and CD24-high cells were subjected to RNA extraction and gene array experiments.

first: Anil

last: Rustgi


title: An intrahepatic gene expression signature of enhanced immune activity predicts response to peginterferon and adefovir in chronic hepatitis B patients

city: Amsterdam

first: Louis

last: Jansen

address: Meibergdreef 9

department: Gastroenterology and Hepatology

country: Netherlands

institute: Academic Medical Center

summary:
In this study we aimed to identify a baseline intrahepatic transcriptional signature associated with response in chronic hepatitis B patients treated with peginterferon-alfa-2a (peg-IFN) and adefovir.
Liver gene expression values of patients with combined response (responders; n=9) and non-response (n=6) were compared for 21,462 annotated gene transcripts. We identified 182 genes which differed on average more than 1.5-fold, of which 53 were relatively upregulated in non-responders and 129 in responders.

overall_design:
15 liver biopsies of chronic hepatitis B patients were selected for RNA extraction and hybridization on Affymetrix microarrays. Expression values in 9 biopsies of patients with a combined response to therapy were compared with 6 biopsies of non-responders.
Differentially expressed genes between responders and non-responders were determined using filtering on minimal average expression, fold change (1.5 fold) and p-values from 2-sided t-tests (0 permutations) in GenePattern.

first: Annikki

last: de Niet

first: Zuzanna

last: Makowska

first: Michael

middle: T

last: Dill

first: Karel

last: van Dort

first: Robert

middle: B

last: Takkenberg

first: Harry

middle: L

last: Janssen

first: Markus

last: Heim

first: Neeltje

last: Kootstra

first: Hendrik

middle: W

last: Reesink


title: Expression data from cells overexpressing c19orf63 (HSS1)

status: Public on Dec 17 2014


title: Primary melanoma tumors from CDKN2A mutation carriers do not belong to a distinct molecular subclass.

city: Lund

first: Göran

last: Jönsson

address: Scheelevägen 8

country: Sweden

institute: Lund University

summary: Analysis of gene expression profiles from sporadic and hereditary primary melanomas. The hypothesis was to test whether any gene expression differences exist between melanomas from CDKN2A mutation carriers and sporadic melanomas.

overall_design: Total RNA was extracted from formalin fixed paraffin embedded tumor tissue blocks. RNA was analysed using the WG-DASL technique.


title: Expression data to investigate Costello syndrome using human iPSCs differentiated into astroglial progenitors and astrocytes

status: Public on Dec 16 2014

last: Krencik

address: 6670 Bertner Ave.

department: Neurosurgery

institute: Houston Methodist

summary:
We used microarrays to compare gene expression between three HRAS-wild type lines (13, 162d, 165d) and three HRAS-G12S mutant lines (7, 8, 16).
Arrays were conducted in all lines from iPSC-derived astroglial progenitors at 8 weeks of differentiation, and in wild-type astrocyte lines at 28 weeks of differentiation.

overall_design: Cells of the astroglial lineage were generated for RNA extraction and hybridization on Affymetrix Human 1.0 ST microarrays.  At each stage, cells were plated as a monolayer and treated with 10ng/ml of CNTF for one week before extraction.

first: Erik

last: Ullian