title: Expression data from skin biopsies in cutaneous T-cell lymphoma

status: Public on Nov 01 2007

first: Jessica

last: Shin

address: 221 Longwood Avenue

institute: Brigham and Women's Hospital

summary:
Cutaneous T cell lymphoma (CTCL) is defined by infiltration of activated and malignant T cells in skin. The clinical manifestations and prognosis in CTCL are highly variable. In this study, we hypothesized that gene expression analysis in lesional skin biopsies can improve understanding of the disease and its management.
Based on 63 skin samples, we performed consensus clustering, revealing three patient clusters. Two clusters tended to differentiate limited CTCL (stages IA and IB) from more extensive CTCL (stages IB and III). Stage IB subjects appeared in both clusters, but those in the limited CTCL cluster were more responsive to treatment than those in the more extensive CTCL cluster. The third cluster was enriched in lymphocyte activation genes and was associated with a high proportion of tumor (stage IIB) lesions. Survival analysis revealed significant differences in event-free survival between clusters, with poorest survival seen in the activated lymphocyte cluster. Using supervised analysis, we further characterized genes significantly associated with lower stage/treatment responsive versus higher stage/treatment resistant CTCL. We conclude that transcriptional profiling of CTCL skin lesions reveals clinically relevant signatures, correlating with differences in survival and response to treatment. Additional prospective long-term studies to validate and refine these findings appear warranted.
Keywords: disease state analysis

overall_design: 63 skin biopsies from patients with different stages of disease were selected for RNA extraction and hybridization on Affymetrix microarrays

first: Stefano

last: Monti

first: Daniel

last: Aries

first: Madeleine

last: Duvic

last: Golub

first: David

last: Jones

first: Thomas

last: Kupper


title: Expression data from age-dichotomized ER+ breast tumors

status: Public on Sep 12 2007

city: Novato

first: Christina

last: Yau

state: CA

address: 8001 Redwood Blvd

country: USA

institute: Buck Institute of Age Research

summary:
To investigate the biological basis between aging and sporadic breast cancer incidence and prognosis, RNA samples from matched ER+ invasive breast cancers diagnosed in either young (≤45) or old (≥70) women were analyzed by expression microarrays
Keywords: biomarker identification

overall_design: ER+ breast cancers collected from either young or old women, well matched for other clinical parameters were analyzed using expression microarrays.  Age associated tumor subtypes and enrichment of pre-defined gene signatures were identified.  Age associated differential expression and an age signature (gene-based classifier) was assessed

first: Vita

last: Fedele

first: Ritu

last: Roydasgupta

first: Jane

last: Fridlyand

first: Alan

last: Hubbard

first: Joe

middle: W

last: Gray

first: Karen

last: Chew

first: Shanaz

middle: H

last: Dairkee

first: Dan

last: Moore

first: Stefania

last: Tommasi

first: Angelo

last: Paradiso

first: Donna

middle: G

last: Albertson

first: Christopher

middle: C

last: Benz


title: Gene expression in pylorus stomach tissue in Bapx1 (Nkx3.2) deficient mice

status: Public on Feb 09 2009

city: College Station

first: Warren

middle: Eugene

last: Zimmer

state: TX

address: 310b J. Reynolds Medical Building

department: Systems Biology and Translational Medicine

institute: Texas A&M Health Science Center

summary:
Bapx1 (Nkx3.2) is an important factor for GI development.  We document a morphologic change in the pylorus segment of the GI tract in Bapx1 deficient mice and we have used microarray analyses to assess gene exprofiles in the pylorus stomach region in knockout compared to wildtype littermates.

Keywords: Genetic modiufied mice deficient in Bapx1 expression

overall_design: RNA from 3 Bapx1 knockout animals and 3 control wildtype littermates were analyzed.

middle: E

first: Monique

middle: N

last: Stanfel


title: Comparison of primary MEF vs HRasV12 + Twist transformed MEF

status: Public on Jul 11 2008

city: Lyon

first: stéphane

last: ansieau

address: 28 rue laennec

country: France

institute: Inserm U590

summary: MEF cells were sequentially infected with H-RasV12 and Twist (Twist1 or Twist2) expression retroviral constructs. Gene expression profiles of the resulting transformed cell lines were compared to the gene expression profile of primary MEF cells

overall_design: Comparison of gene expression profile

first: Stéphane

last: Ansieau

first: Jérémy

last: Bastid

first: Agnès

last: Doreau

first: Alain

last: Puisieux

first: Joël

last: Lachuer


title: Dox-regulated Notch4 overexpression in mouse ES cells redirects hemagioblasts to a cardiac fate.

status: Public on Sep 28 2008

city: South San Francisco

first: Robert

middle: A

last: Stull

address: 384 Oyster Point Blvd, Suite #8

department: Genomics

institute: VistaGen Therapeutics

summary:
Previous studies have demonstrated that distinct progenitor subpopulations of mesoderm display tissue specific and vascular potential: hemangioblasts, a progenitor population capable of generating cells of the hematopoietic, endothelial and vascular smooth muscle lineages, and a multipotential progenitor capable of generating progeny of the cardiac, endothelial and vascular smooth muscle lineages.  Each of these populations is characterized by co-expression of brachyury (Bry) and Flk-1, although the hemangioblast population is established before the cardiovascular progenitors in ES cell differentiation cultures (e.g. d3.5 for hemagioblast, versus d4.5 for cardiovascular progenitors).
To investigate the role of Notch signalling in the establishment of cardiac lineages, we used a tet-inducible ES cell line (Ainv18) engineered to express an activated form of the Notch4 receptor following doxycycline treatment. This line also expresses a GFP cDNA from the Bry locus. Following 3.0-3.5 days of serum stimulation, three distinct populations based on Flk-1 and GFP expression are observed: Bry-GFP-/Flk-1-, Bry-GFP+/Flk-1- and Bry-GFP+/Flk-1+ cells.  Previous studies have shown that the Bry-GFP+/Flk-1+ population contains hemangioblasts, whereas the Bry-GFP+/Flk-1- population displays cardiac potential.

overall_design: Bry-GFP+/Flk-1+ cells, sorted from EB's derived from ES cell differentiation cultures exposed to serum for 3.5 days, were allowed to reaggregate for 24 in the presence or absence of doxycycline, and the total RNA harvested at 4, 12, 24, 48, and 96 hours post Dox induction for microarray analysis.  The induced populations were compared to non-induced population harvested at the same time points.

first: VincentC

last: Chen

first: Daniel

last: Joo

first: Xin

last: Cheng

first: Gordon

last: Keller


title: Kidney Expression Profiles MT

status: Public on Jun 07 2007

city: Heidelberg

first: Mathias

last: Treier

address: Meyerhofstrasse 1

department: Developmental Biology Unit

country: Germany

institute: EMBL

summary:
comparison of wiltype and homozygous mutant kidney RNA expression profiles at 4 weeks of age
Keywords: wildtype-knockout comparison

overall_design: 3 biological replicates per genotype (3 different animals): 3 wildtype and 3 homozygous mutant mice, resulting in 6 chips total


title: Expression data from age-dichotomized ER+, N0 breast tumors

status: Public on Apr 02 2007

first: Christina

last: Yau

summary:
Signaling pathways that converge on two different transcription factor complexes, NFκB and AP-1, have been identified in estrogen receptor (ER)-positive breast cancers resistant to the antiestrogen, tamoxifen.
In this study, biomarkers co-ordinately up-regulated by NFKB and AP-1 with prognositic significance are identified in a largely TAM-treated set of ER+ node negative breast cancers.  The prognostic value with respect to age is also investigated.
Keywords: biomarker identification

overall_design: 54 ER+ node negative breast tumors with known clinical outcome were analyzed.  Genes co-ordinately regulated by NFKB and AP1from literature are identified from a significant gene set obtained through a minimum variation filter.  Biomarker expression is used to dichotomize samples into high vs. low expressors to determine prognostic value

first: Yamei

last: Zhou

first: Joe

last: Gray

first: Karen

last: Chew

first: Shanaz

last: Dairkee

first: Dan

last: Moore


title: Microarray analysis  of in vivo inhibition of mir-122 with an antisense oligonucleotide.

status: Public on Mar 01 2006

city: Carlsbad

first: Michael

last: Pear

address: 1896 Rutherford Rd

department: Research Informatics

institute: Isis Pharmaceuticals, Inc.

summary:
Current understanding of microRNA (miRNA) biology is limited, and antisense oligonucleotide (ASO) inhibition of miRs is a powerful technique for their functionalization.  To uncover the role of the liver-specific miR-122 in the adult liver, we inhibited it in vivo using a 2’-O-methoxyethyl phosphorothioate ASO.  This microrarray experiment was used to identify changes in mRNA levels due to the inhibition of miR-122 that accompanied phenotypic observations of reduced cholesterol and triglycerides, increased fatty acid oxidation, and decreased fatty acid and cholesterol synthesis rates observed in hepatocytes.
Keywords: single treatment vs. control

overall_design: The experiment contains two groups of 5 mice: one group treated with an antisense to miR-122, and a second group injected only with saline as a control. RNA was extracted from individual livers, and each of these samples was hybridized to a single-channel chip. The design was intended to permit determination of statistically significant fold changes 1.5 and above.

first: Christine

last: Esau


title: p400/mDomino-deficient mouse embryo proper

status: Public on Nov 20 2006

city: Suita

first: Rikiro

last: Fukunaga

state: Osaka

address: 2-2 Yamadaoka

department: Grad School Frontier Biosciences

country: Japan

institute: Osaka University

summary:
The SWI2/SNF2 family ATPase, p400/mDomino, is a core subunit of a large chromatin-remodeling complex. The mDomino-deficient (mDom-/-) mice died by embryonic day 11.5, and displayed an anemic appearance and slight deformity of the neural tube. We examined the gene expression in the wild-type (GSM121658) and mDom-/- (GSM121659) E8.5 embryo proper, and found that all of the embryonic globin genes and a globin chaperone gene (AHSP) were poorly expressed in the mDom-/- embryo on embryonic day 8.5.
Keywords: Comparative gene expression analysis of wild-type and gene-targeted mice

overall_design: Total RNA was prepared from mixtures of litter-matched embryos at E8.5 (wild-type embryos: n = 42, mDom-/- embryos: n = 45).

first: Takeshi

last: Ueda

first: Rie

last: Watanabe-Fukunaga

first: Hironori

last: Ogawa

first: Hidehiro

last: Fukuyama

first: Yujiro

last: Higashi

first: Shigekazu

last: Nagata


title: Expression profiling of secreted and cell surface genes of 5 transformed cell lines and derivative xenograft tumors

status: Public on Jan 25 2005

city: Menlo Park

first: Daniel

middle: J

last: Chin

institute: PPD Discovery

summary:
Since the early stages of tumorigenesis involve adhesion, escape from immune surveillance, vascularization and angiogenesis, we devised a strategy to study the expression profiles of all publicly known and putative secreted and cell surface genes. We designed a custom oligonucleotide microarray containing probes for 3531 secreted and cell surface genes to study 5 diverse human transformed cell lines and their derivative xenograft tumors. The origins of these human cell lines were lung (A549), breast (MDA MB-231), colon (HCT-116), ovarian (SK-OV- 3) and prostate (PC3) carcinomas. Three different analyses were performed: (1) A PCA-based linear discriminant analysis identified a 54 gene profile characteristic of all tumors when pooled tumor data were analyzed, (2) Application of MANOVA (P Pcorr corr < .05) to pooled tumor data revealed a larger set of 149 differentially expressed genes. (3) After MANOVA was performed on data from individual tumors, a comparison of differential genes amongst all tumor types revealed 12 common differential genes. Seven of the 12 genes were identified by all three analytical methods. These included late angiogenic, morphogenic and extracellular matrix genes such as ANGPTL4, COL1A1, GP2, GPR57, LAMB3, PCDHB9 and PTGER3. The differential expression of ANGPTL4 and COL1A1 and other genes was confirmed by quantitative PCR. Overall, a comparison of the three analyses revealed an expression pattern indicative of late angiogenic processes. These results show that a xenograft model using multiple cell lines of diverse tissue origin can identify common tumorigenic cell surface or secreted molecules that may be important biomarker and therapeutic discoveries.
Keywords: parallel sample

first: Robert

last: Stull

first: Roya

last: Tavassoli

first: Scot

last: Kennedy

first: Steve

last: Osborn

first: Rachel

last: Harte

first: Yan

last: Lu

first: Cheryl

last: Napier

first: Arie

last: Abo


title: Gene expression analysis of rat livers after exposure to acetaminophen

status: Public on Sep 19 2006

city: RTP

first: NIEHS

last: Microarray Core

state: NC

address: 111 T.W. Alexander Drive

department: DIR

institute: NIEHS

summary:
Male F344 rats were expsoed to sub-toxic (50 or 150 mg/kg) or toxic (1500 or 2000 mg/kg) doses of acetaminophen. RNa was extracted from livers and gene expression analysis was performed on Agilent rat oligonucleotide chips.
Keywords: Competitive hybridization

overall_design: Individual treated animal RNA was compared to control animal pooled RNA.

first: Alexandra

last: Heinloth

first: Richard

middle: S

last: Paules


title: Wildtype Mouse Hypothalamus Cerebellum Fed Fast

status: Public on Feb 09 2007

city: Cambridge

first: Keira

last: Curtis

address: Box 232, Addenbrooke's Hospital, Hills Road

department: Clinical Biochemistry

country: United Kingdom

institute: University of Cambridge

summary:
The hypothalamus is a key site for the integration of the response to nutrient deprivation in higher organisms.  Transcripts that are dynamically regulated in the hypothalamus by feeding and fasting are likely to play a regulatory role in energy balance.  In order to identify hypothalamic genes whose expression is altered by fasting, we compared the transcriptomes of hypothalamic blocks from freely feeding vs overnight fasted mice using whole genome oligonucleotide arrays.  In order to exclude changes due to non-specific neuronal stress responses to energy deprivation we simultaneously profiled the cerebellum, a brain site with no known regulatory role in energy balance. The power of this approach was illustrated by the fact that while we confirmed previous observations that the Sulfotransferase family 1A gene is upregulated by fasting in the hypothalamus, we showed that it was similarly upregulated in the cerebellum and is therefore unlikely to be specifically involved in the regulation of energy balance. In contrast, using three different methods of pathway enrichment analysis, multiple genes involved in mitochondrial oxidative phosphorylation were found to be co-ordinately downregulated by fasting in the hypothalamus but not in the cerebellum. These findings suggest that a switch from oxidative to non-oxidative metabolism in the hypothalamus may be an important element of the homeostatic response to nutrient deprivation.
Keywords: hypothalamus, cerebellum, fasting, appetite, obesity

overall_design: Wild-type female SV/129 mice were purchased from Charles River.  At onset of the dark phase the evening before the experiment, food was removed from one group of 6 mice; while a further 6 animals were allowed continued access to chow.  Both groups had ad libitum access to water.  The next morning (16 hours later), mice were sacrificed by cervical dislocation and decapitated.   The brains were removed and the hypothalami and cerebellar slices were rapidly dissected and snap frozen on powdered dry ice.  Purified RNA from each condition and brain region was pooled resulting in 4 different sample groups (Fed & Fasted; hypothalamus & cerebellum).  Double stranded cDNA was generated from 2μg of total RNA from each sample group, converted to cRNA and biotin labelled using the Codelink Expression Assay Reagent Kit (GE Healthcare).   10μg of biotin labelled cRNA was hybridized overnight onto CodeLink™ Mouse Whole Genome Bioarrays (GE Healthcare) according to manufacturer’s protocols.  Each RNA sample group was hybridized in triplicate.  One Cerebellum Fast chip was discarded because it failed QC.

first: R.

middle: K

first: Yi-Chun

middle: L

last: Tung

first: Sarah

last: Piper

first: Anthony

middle: P

last: Coll

first: Stephen

last: O'Rahilly

first: Giles

last: Yeo