title: Forkhead Box F1 (FOXF1) represses fibroblast functions relevant to fibrogenesis

status: Public on Oct 01 2014

city: Valbonne - Sophia-Antipolis

first: Kevin

last: Lebrigand

address: 660 route des lucioles

institute: IPMC/CNRS

summary: Aberrant expression of master phenotype regulators by lung fibroblasts may play a central role in idiopathic pulmonary fibrosis (IPF). Interrogating IPF fibroblast transcriptome datasets, we identified Forkhead Box F1 (FOXF1), a DNA-binding protein required for lung development, as a candidate actor in IPF. Thus, we determined FOXF1 expression levels in fibroblasts cultured from normal or IPF lungs in vitro, and explored FOXF1 functions in these cells using transient and stable loss-of-function and gain-of-function models. FOXF1 mRNA and protein were expressed at higher levels in IPF compared with controls. In normal lung fibroblasts, FOXF1 repressed key fibroblast functions such as proliferation, survival, and expression of collagen-1 (COL1) and actin related protein 2/3 complex, subunit 2 (ARPC2). ARPC2 knockdown mimicked FOXF1 overexpression with regard to proliferation and COL1 expression. FOXF1 expression was induced by the antifibrotic mediator prostaglandin E2 (PGE2). Ex vivo, FOXF1 knockdown conferred CCL-210 lung fibroblasts the ability to implant and survive in uninjured mouse lungs. In IPF lung fibroblasts, FOXF1 regulated COL1 but not ARPC2 expression. In conclusion, FOXF1 functions and regulation were consistent with an antifibrotic role in lung fibroblasts. Higher FOXF1 levels in IPF fibroblasts may thus participate in a compensatory response to fibrogenesis.

overall_design: Lung fibroblasts derived from 4 different IPF patients (P313, P355, P375 and P426) were transiently transfected with pcfoxf1 or control pcDNA3.1-constructs. Total RNAs were extracted 24 h after transfection and hybridized on microarrays. One color experiment with 2 experimental conditions: pcfoxf1 and pcDNA3.1

first: L

last: Plantier

first: I

last: Henaoui

first: B

last: Mari

first: K

first: P

last: Barbry


title: Gene expression microarray and CGH array of metabolically adaptable cells derived from SUM149 triple-negative Inflammatory Breast Cancer cell line

status: Public on Oct 03 2014

city: Houston

first: Anthony

last: Lucci

state: Texas

address: 1515 Holcombe Blvd

department: Surgical Oncology

country: USA

institute: UT MD Anderson Cancer Center

type: Genome binding/occupancy profiling by genome tiling array

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

overall_design: Refer to individual Series


title: Prediction of prognosis for small cell lung cancer based on genome-wide methylation analyses with surgical materials and robust clustering methods

status: Public on Oct 04 2014

city: Koto

first: YUICHI

last: SAITO

state: Tokyo

address: 3-8-31 Ariake

department: Pathology

country: Japan

institute: The Cancer Institute of Japanese Foundation Cancer Research

summary:
Methylation is closely involved in the development of various carcinomas. However, little datasets are available for small cell lung carcinoma (SCLC) due to the scarcity of fresh tumor samples. The aim of this study is to investigate the comprehensive genome-wide methylation profile of SCLC to predict the prognosis after surgical treatment.
We investigated the high DNA methylated and low gene expression sites using 25 SCLC tumor tissues. First, we selected most differentially methylated CpG sites across the tumor tissues. Following hierarchical clustering (HC) and non-negative matrix factorization (NMF), gene ontology analysis was performed using DAVID software. Clustering of SCLC tumors led to the important identification of a CpG island methylator phenotype (CIMP) of SCLC, and showed that CIMP-high tumors had a significantly poorer prognosis (p = 0.001). Multivariate analysis revealed that postoperative chemotherapy, low neuroendocrine expression and the CIMP-low state were significantly good prognostic factors. Association analyses of methylation and gene expression provided 46 genes with significant correlation. Ontology studies to these genes showed that genes involved in extrinsic apoptosis pathway were suppressed, including TNFRSF1A, TNFRSF10A and TRADD, in CIMP-high tumors, prognosis of which was poorer. By comprehensive DNA methylation profiling, two distinct subgroups were identified to evoke a CIMP of SCLC as a useful marker for determination of treatment. Delineation of this phenotype may also be useful for the development of novel apoptosis-related chemotherapeutic agents for the treatment of an aggressive subtype of SCLC.

overall_design: Comprehensive genome-wide methylation analyses

first: Yuichi

last: Saito

last: Ishikawa


title: SNP genotyping data from human iPSCs and human fibroblast cells

status: Public on Sep 26 2014

city: Cambridgeshire

first: Yichen

last: Shi

address: Suite 3, The Science Village Building, Chesterford Research Park, Little Chesterford

country: United Kingdom

institute: Axol Bioscience Limited

summary: Human induced pluripotent stem cells changed the face of stem cell biology as they represent a renewable source of stem cells with the potential to differentiated into multiple lineages in a manner akin to embryonic stem cells that can be collected without the need for the destruction of an embryo. The potential of these cells as research tools is vast as they can be pushed to generate different cell types depending on research interest. Many complex diseasese.g. late onset alzheimer's disease and type 2 diabetes have known genetic risk factors that increase the likelihood of developing a disease. We performed whole genome SNP analysis to examine risk loci for different complex diseases in our donor iPS cells toanalyse disease risk and also assess which donor represents the best healthy background.

overall_design: Genomic DNA was isolated from human induced pluripotent stem cells from 3 donors and fibroblasts from an additional donor for genome-wide SNP analysis. This study was completed using the Affymetrix human genome-wide array 6.0 and analysed using the Affymetrix Genotyping Console Birdseed V2 algorithm.

first: Jun

last: Wei

first: Claire

last: Cox


title: Effects of Long-term Serial Passaging on the Characteristics and Properties of Cell Lines Derived From Uveal Melanoma Primary Tumors.

status: Public on Sep 09 2014

city: Québec

first: Karine

last: Zaniolo

state: Québec

address: 1050 Chemin Sainte-Foy

department: CUO-Recherche

country: Canada

institute: Centre de recherche du CHU de Québec

summary: Development of liver metastasis remains the most common cause of mortality in uveal melanoma (UM). Although advances in genomics allowed the direct evaluation of clinical samples of this eye cancer, there is still a need for reliable preclinical models to progress from correlative studies to mechanistic investigations. A few UM cell lines have been characterized, but so far the translation of basic knowledge to the clinic for the treatment of metastatic disease has been incremental at best. The aim of this study was to determine whether the properties of UM cell lines at various passages were similar to their corresponding primary tumors.

overall_design: Two primary uveal melanoma tumors and their derivative cell lines at three different passages are analyzed by gene profiling

first: Frédéric

last: Mouriaux

first: Marjorie

middle: A

last: Bergeron

first: Cindy

last: Weidmann

first: Arnaud

last: De La Fouchardière

last: Fournier

last: Droit

first: Mohib

middle: W

last: Marcos

first: Solange

last: Landreville

first: Sylvain

middle: L

last: Guérin


title: Gene expression of metabolically adaptable triple-negative breast cancer cells

last: Lucci

summary: To gain insight into the characteristic of metabolically adaptable MA cells that enables them to survive severe metabolic challenge, i.e., prolonged lack of glutamine and other challenges [Singh et al., PLoS ONE 7: e36510, 2012], we used gene expression microarrays to compare these cells with the parental SUM149-Luc (luciferase-transfected) cells. We analyzed two independently selected cell populations, one from 0.5 million parental cells (designated MA1) and one from 1 million parental cells (designated MA2).

overall_design: Comparing MA1 and MA2 variants to a common parental cell line SUM149-Luc. One sample each.

first: Balraj

last: Singh


title: Gene expression profile of HoxA9 over expressing and empty vector (EV) control Hemato-Endothelial Progenitors (HEPs) subpopulations

status: Public on Sep 03 2014

city: Granada

first: Pedro

middle: Jose

last: Real

state: Granada

address: Avda. Ilustracion 114

department: Molecular Oncology

country: Spain

institute: GENyO

summary: During hematopoietic differentiation of hESCs, HOXA9 expression parallels hematopoietic development but is restricted to the hemogenic precursors (HEP, CD31+CD34+CD45-), and diminishes as HEPs differentiate into blood cells (CD45+). Enforced expression of Hoxa9 in hESCs robustly promoted differentiation into primitive (CD34+CD45+) and total (CD45+) blood cells with higher clonogenic (CFU) potential. To identify patterns of gene expression that could explain at the molecular level the developmental impact of HOXA9 in hematopoietic commitment of hESCs, we  performed gene expression profile in FACS-purified EV- and HOXA9-HEPs.

overall_design: 10^5  HoxA9 over expressing and EV control HEPs purified by FACS from H9 and AND1 hEBs at day 15 of hematopoietic differentiation were used for gene expression analysis using Whole Human Genome Oligo Microarray chips (Agilent Technologies).

first: Veronica

last: Ramos-Mejia

first: Pablo

last: Menendez


title: Expression data from U373 cell lines

status: Public on Sep 01 2014

city: Mexico City

first: Ivan

last: Salido-Guadarrama

address: Calz. de Tlalpan 4502

country: Mexico

institute: Instituto Nacional de Enfermedades Respiratorias

summary: Intracellular progesterone receptor (PR) presents two main isoforms: PR-A and PR-B with different function and regulation. Both isoforms have been identified in astrocytomas, the most common and aggressive primary brain tumors in humans. To investigate the role of PR activity in the regulation of gene expression pattern of U373 cells, we evaluated by microarray analysis the profile of genes regulated by progesterone (10 nM), by a progesterone receptor antagonist (RU486, 10 µM) or by both steroids.

overall_design: The human astrocytoma cell line U373 was treated with progesterone; the antagonist, RU-486 or a combination of both drugs.Subsecuently, total RNA was extracted and hybridised on Affymetrix Human Gene 1.0 STs.

first: Aliesha

last: González-Arenas

first: Alejandro

last: Cabrera-Wrooman

first: Nestor

middle: F

last: Díaz

first: Tania

middle: K

last: González-García

first: A

middle: I

first: Mauricio

last: Rodríguez-Dorantes

first: Ignacio

last: Camacho-Arroyo


title: Genetic Copy Number Variants in Myocardial Infarction Patients with Hyperlipidemia

status: Public on Aug 09 2014

city: Changhua City

first: Wei-Chung

last: Shia

address: 8F., No.235, Xuguang Rd.

department: Cancer Research Center

country: Taiwan

institute: Changhua Christian Hospital

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

summary:
We identified 7 CNV regions that were associated significantly with hyperlipidemia and myocardial infarction in our patients through multistage analysis (P<0.001).
The inclusion criteria for enrolling patients were drawn from the Prospective Cardiovascular Munster study [http://www.ncbi.nlm.nih.gov/pubmed/3202078] and Framingham Heart Study [http://www.ncbi.nlm.nih.gov/pubmed/9737513]. In brief, patients aged between 20 and 75 years with coronary arterial disease with more than 50% stenosis, as proven by cardiac catheterization, and a history of hyperlipidemia with serum cholesterol level greater than 240 mg/dL or low-density lipoprotein greater than 155 mg/dL were enrolled.

overall_design: Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from whole blood samples. 40 Samples.

first: Tien-Hsiung

last: Ku


title: Selection of epigenetic variation in Arabidopsis [Expression]

city: Zürich

first: Christian

last: Heichinger

state: Zürich

address: Zollikerstrasse 107

department: Institute of Plant Biology

country: Switzerland

institute: Zürich University

summary: In Arabidopsis thaliana a high rate of spontaneous epigenetic variation can occur in the DNA methylome in the absence of genetic variation and selection. It has been of great interest, whether natural epigenetic variation is subject to selection and contributes to fitness and adaptation in selective environments. We compared the variation in selected phenotypic traits, genome-wide cytosine DNA methylation and gene expression in two Arabidopsis recombinant inbred lines, which had undergone five generations of selection in experimental landscapes relative to their genetically identical ancestors. Selected populations exerted significant differences in flowering time and the number of branches and fruits, differences that were maintained over two to three generations in the absence of selection. We identified 4,629 and 5,158 differentially methylated cytosines which were overrepresented in genes that regulate flowering time, epigenetic processes, development and morphogenesis. Differentially methylated genes were enriched in differentially expressed genes. Thus, epigenetic variation is subject to selection and may play an important role in the adaptive response of populations in rapidly changing natural environments.

overall_design: Whole plant tissue from 25-day old plants was used for RNA extractions. RNA was extracted from 4 plants of each genotype (CVL39 and CVL125) from ancestral lines (A2) = Reference sample (4 biological replicates), and lines that had experienced 5 generations of selection in dynamic landscapes  (S2) = Test sample (4 biological replicates); average signal ratios were compared.

first: Marc

last: Schmid

first: Daniela

last: Kleen

first: Remy

last: Bruggmann

first: Sirisha

last: Aluri

first: Marzanna

last: Künzli

first: Lindsay

last: Turnbull

first: Bernhard

first: Ueli

last: Grossniklaus


title: DNA copy number detection from exome sequencing - Exploiting the off-targets (SNP)

status: Public on Aug 12 2014

city: Amsterdam

first: Oscar

last: Krijgsman

state: Outside the US or Canada

address: Plesmanlaan 121

department: Molecular Oncology and Immunology

country: Netherlands

institute: Netherlands Cancer Institute

summary:
Current methods for detection of copy number aberrations (CNA) from whole-exome sequencing (WES) data are based on the read counts of the captured exons only. However, accurate CNA determination is complicated by the non-uniform read depth and uneven distribution of exons. Therefore, we developed ENCODER (ENhanced COpy number Detection from Exome Reads), which eludes these problems. By exploiting the ‘off-target’ sequence reads, it allows for creation of robust copy number profiles from WES. The accuracy of ENCODER compares to approaches specifically designed for copy number detection, and outperforms current exon-based WES methods, particularly in samples of low quality.  Current methods for detection of copy number aberrations (CNA) from whole-exome sequencing (WES) data are based on the read counts of the captured exons only. However, accurate CNA determination is complicated by the non-uniform read depth and uneven distribution of exons. Therefore, we developed ENCODER (ENhanced COpy number Detection from Exome Reads), which eludes these problems. By exploiting the ‘off-target’ sequence reads, it allows for creation of robust copy number profiles from WES. The accuracy of ENCODER compares to approaches specifically designed for copy number detection, and outperforms current exon-based WES methods, particularly in samples of low quality.  Current methods for detection of copy number aberrations (CNA) from whole-exome sequencing (WES) data are based on the read counts of the captured exons only. However, accurate CNA determination is complicated by the non-uniform read depth and uneven distribution of exons. Therefore, we developed ENCODER (ENhanced COpy number Detection from Exome Reads), which eludes these problems. By exploiting the ‘off-target’ sequence reads, it allows for creation of robust copy number profiles from WES. The accuracy of ENCODER compares to approaches specifically designed for copy number detection, and outperforms current exon-based WES methods, particularly in samples of low quality.
DNA copy number profiles generated with a new tool, ENCODER, were compared to DNA copy number profiles from SNP6, NimbleGen and low-coverage Whole Genome Sequencing.

overall_design: DNA copy number profiles of melanoma PDX sample were generated with ENCODER from whole exome sequencing data and compared to results from the SNP6 platform.

first: T

last: Kuilman

first: O


title: Genome-wide analysis of the effects of the novel mithramycin analogue DIG-MSK on human A2780 ovarian carcinoma cells

status: Public on Aug 13 2014

city: Barcelona

first: José

last: Portugal

address: Parc Cientific de Barcelona, Baldiri Reixac, 10

department: Molecular Genomics

institute: Instituto de Biologia Molecular  de Barcelona-CSIC

summary: The effects of demycarosyl-3D-β-D-digitoxosyl-mithramycin SK (DIG-MSK; EC-8042), a novel analogue of the antitumor antibiotic mithramycin A, on gene transcription were examined in human A2780 ovarian carcinoma cells. DIG-MSK down-regulated a different set of genes depending on the drug concentration. Moreover, several genes were significantly up-regulated. These results are rationalized in terms of DIG-MSK competition with Sp1 transcription factor for binding to consensus C/G-rich tracts encompassed in gene promoters.

overall_design: Human A2780 ovarian carcinoma cells were treated with either 8 nM or 80 nM DIG-MSK for 24 h, and RNA was extracted from treated cells as well as from untreated (control) cells.

first: Carolina

last: Vizcaíno

first: Francisco

last: Morís


title: DNA copy number detection from exome sequencing - Exploiting the off-targets

type: Genome variation profiling by genome tiling array

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: Expression profiles of pheochromocytoma and paraganglioma

status: Public on Aug 17 2014

city: Seoul

first: Yoon-La

last: Choi

address: 81 Irwon-Ro, Gangnam-gu

department: Department of pathology

country: South Korea

institute: Samsung medical center

summary: Until now, it is nearly impossible to diagnose malignancy of peochormocytoma/paraganglioma with pathological examinations. The aim of the study is to find the genes which can be applied as a biomarker in the clinic to distinguish benign and malignant forms of pheochromocytoma/paraganglioma.

overall_design: We generated exprssion profiles of 9 samples of benign tumors, 3 samples of malignant tumors and 3 samples of normal adrenal medulla.

first: Yool-La

first: Seung

middle: E

last: Lee

first: Ensel

last: Oh

first: Ji

middle: Y

last: Song

first: Eunseo

last: Ahn


title: NQO1 regulates inflammatory signaling

status: Public on Aug 26 2014

city: San Antonio

first: Rita

last: Ghosh

state: TX

address: 8403 Floyd Curl Drive

department: Urology

institute: University of Texas Health Science Center at San Antonio

summary: NQO1 silencing by a specific shRNA against NQO1 increased migration and hormone-independent survival in hormone-dependent human prostate cancer cells LNCaP. Genome wide array revealed that NQO1 blockade significantly upregulated pro-inflammatory mediators (e.g., IL-32, CCL2, IL-8, IL-17C, IL-10RA, CXCR2, CXCR7, NOS3) associated with prostate tumorigenesis.

overall_design: Two-condition experiment, control vs. NQO1 knockdown LNCaP cells. Biological replicates: 3 control replicates, 3 NQO1 knockdown replicates.

first: Dinesh

last: Thapa

first: Peng

last: Meng

first: Roble

middle: G

last: Bedolla

first: Robert

last: Reddick

first: Addanki

middle: P

last: Kumar


title: Single Nucleotide Polymorphisms Other Than Factor V Leiden are Associated with Coagulopathy and Osteonecrosis of the Femoral Head in Chinese Patients

status: Public on Jul 28 2014

city: TauYau

first: Yun-Shien

state: Taiwan

address: TauYau

department: Dept. Biotechnology

institute: Ming Chuan Univ

summary: Single nucleotide polymorphisms (SNPs) of factor V Leiden have been associated with osteonecrosis of the femoral head (ONFH) in Caucasians but remains controversial in Asians. We used an SNP microarray to screen 55 loci of factor V gene in patients with ONFH of Chinese. Significantly different candidate SNPs at 14 loci were analyzed in 146 patients and 116 healthy controls using MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry and gene sequencing. The factor V Leiden (rs6025) was not found in all participants. Six SNP loci (rs9332595, rs6020, rs9332647, rs3766110, rs10919186, and rs12040141) were confirmed with significant differences in patients but not in controls. The rs6020 G-to-A polymorphism was found in 88.9% of the patients. In addition, a high percentage (84.7%) of the patients had an abnormal coagulation profile that included hyperfibrinogen, elevated fibrinogen degradation products, elevated D-dimer, abnormal protein S, abnormal protein C, or a decrease in anti-thrombin III. Patients with the rs6020 G-to-A polymorphism (mutation) had a higher risk (odds ratio: 4.33; 95% confidence interval: 1.36-13.76) of having coagulation abnormalities than did those without the mutation (wild-type) (p = 0.008). Our findings suggested that the rs6020 polymorphism might be the genetic trait that accounts for the higher prevalence of ONFH in the Chinese population than in Westerners. Exposure to risk factors such as alcohol and steroids in patients with the rs6020 polymorphism causes coagulation abnormalities and, subsequently, thromboembolisms in the femoral head.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from peripheral blood samples.
SNP genotype analysis of Affymetrix 6.0 Chip. SNP arrays was performed for 22 Chinese patients with Osteonecrosis of the Femoral Head.

first: Kou-ti

last: Peng

first: Kuo-Chin

last: Hwang

first: Tsaang-Wen

first: Wei-Hsiu

last: Hsu

first: Steve

last: Ueng

first: Mel

middle: S


title: Expression and copy number profiles of pheochromocytoma and paraganglioma

first: Yoon-La

type:
Genome variation profiling by array
Expression profiling by array


title: Genome-wide analysis in Human Colorectal Cells reveals Ischaemia-mediated expression of motility genes via DNA hypomethylation (SNP array)

status: Public on Jul 07 2014

city: Guelph

first: Brenda

last: Coomber

state: Ontario

address: 50 Stone Road

department: Department of Biomedical Sciences

institute: University of Guelph

summary: DNA hypomethylation is an important epigenetic modification found to occur in many  different cancer types, leading to the upregulation of previously silenced genes and  loss of genomic stability. We previously demonstrated that hypoxia and  hypoglycaemia (ischemia), two common micro-environmental changes in solid tumors,  decrease DNA methylation through the downregulation of DNMTs in human colorectal  cancer cells. Here, we utilized a genome-wide cross-platform approach to identify  genes hypomethylated and upregulated by ischemia. Following exposure to hypoxia or  hypoglycaemia, methylated DNA from human colorectal cancer cells (HCT116) was  immunoprecipitated and analysed with an Affymetrix promoter array. Additionally, RNA  was isolated and analysed in parallel with an Affymetrix expression array. Ingenuity  pathway analysis software revealed that a significant proportion of the genes  hypomethylated and upregulated were involved in cellular movement, including PLAUR  and CYR61. A Matrigel invasion assay revealed that indeed HCT116 cells grown in  hypoxic or hypoglycaemic conditions have increased mobility capabilities. Confirmation  of upregulated expression of cellular movement genes was performed with qPCR. The  correlation between ischemia and metastasis is well established in cancer progression,  but the molecular mechanisms responsible for this common observation have not been  clearly identified. Our novel results suggest that hypoxia and hypoglycaemia may be  driving changes in DNA methylation through downregulation of DNMTs. This is the first  report to our knowledge that provides an explanation for the increased metastatic  potential seen in ischemic cells; i.e. that ischemia could be driving DNA  hypomethylation and increasing expression of cellular movement genes.

overall_design: Genomic DNA from the Human Colorectal cancer Cell line HCT116 was hybridized in duplicate to Affymetrix Human SNP 6.0 arrays.  CNVs were determined by comparison to 270 sample HAPMAP data.

first: Karolina

last: Skowronski

first: Joseph

last: Andrews

first: David

last: Rodenhiser


title: Comparative genomic hybridization of CHO Chr6 cell line

status: Public on Jun 05 2014

city: Würzburg

first: Claus

middle: Juergen

last: Scholz

address: Josef-Schneider-Str. 2

department: Core Unit SysMed

country: Germany

institute: University Hospital Würzburg

summary: Aim is to validate content of human genomic material in CHO cells monosomal for human chromosome 6.

overall_design: Comparative genomic hybridization to define human genomic regions maintained in hamster hybridoma cell line.

first: Mohindar

middle: M

last: Karunakaran

middle: J

first: Thomas

last: Herrmann


title: The pattern of genomic instability during bladder cancer progression (part 2)

status: Public on Jul 01 2014

city: Aarhus N

first: Philippe

last: Lamy

address: Brendstrupgårdsvej 100

department: Department of molecular medecine

country: Denmark

institute: MOMA

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

summary: The Affymetrix SNP6.0 arrays were done for two metachronous tumors and the blood from three patients. It was used to define copy number abnormalities in order to support subclonal population analysis in this patient.

overall_design: Nine samples were analysed concerning two metachronous tumor samples and a blood sample from the three different patients.

first: Iver

last: Nordentoft


title: Whole Genome Characterization of Circulating Tumor Cells Identifies Novel Prognostic Genomic Alterations in Melanoma Metastasis

city: Santa Monica

first: Neal

middle: Percy

last: Kawas

state: CA

address: 2200 Santa Monica Blvd

institute: John Wayne Cancer Institute

summary:
Circulating tumor cells (CTCs) are critical in the development of distant organ tumor metastasis, and are associated with advanced cancer stage and poor patient outcome. Here, we present the first genome-wide nucleotide-level characterization of CTCs. Our single-nucleotide polymorphism (SNP) analysis in patients with melanoma involved: 1) global comparative genomic analysis of CTCs and matched regional metastases, 2) identification of key genomic aberrations in CTCs, 3) verification of these target genes in aggressive distant tumor metastases, and 4) evidence of selective expression and functional consequence of CTC-associated genes in melanomas. We report 131 aberrant loci in CTCs that are potentially pro-metastatic, and show that such expression of a 5-marker gene panel (CSMD2, CNTNAP5, FLJ14051, ADAM6, TRPM2) in melanomas confers prognostic utility.

Successful treatment of melanoma requires understanding of the metastatic process and identification of patients with tumors most likely to develop aggressive metastatic disease. Melanomas are heterogeneous, and CTCs have long been recognized as vehicles for cancer spread, representing particularly aggressive tumor clones that can evolve into successful clinical metastases. Elucidation of genomic aberrations in CTCs will aid in the development of prognostic biomarkers and therapeutic strategies to target CTCs to prevent or control distant cancer spread. This study provides the first detailed genomic confirmation of the close relation between CTCs and tumor metastases, and illustrates how CTCs can be utilized as a novel approach and rational source for identification of pro-metastatic genes in cancer research.

overall_design: Three individual patient cohorts were utilized in the study. CNV and LOH loci were evaluated initially in metastatic melanoma patients (n=13) in a discovery cohort. SNP loci that harbored CNV/LOH in CTCs were then separately verified for: (a) presence in distant organ metastasis (AJCC Stage IV melanoma) (n=27), and (b) relevance to prognosis in regional melanoma metastasis (AJCC Stage III melanoma) (n=35). The first discovery patient cohort group was utilized for capture of CTCs, and consisted of peripheral blood mononuclear cell (PBMC) and tumor specimens from metastatic melanoma patients (n=13). CTC-related loci were verified in a second cohort of patients with Stage IV distant organ metastases (n=27), including 15 brain, 4 lung, and 8 gastrointestinal (bowel, liver) metastases. The third patient cohort consisted of early passage (<12) established melanoma cell lines derived from 35 regional melanoma metastases (Stage III) for evaluation of the prognostic utility of the CTC-associated aberrant loci.

first: Connie

last: Chiu

first: Yoshitaka

last: Nakamura

first: Kelly

last: Chong

first: Sharon

last: Huang

first: Timothy

last: Triche

last: Elashoff

first: Eiji

last: Kiyohara

first: Reiko

last: Irie

first: Donald

last: Morton

first: Dave

last: Hoon


title: The pattern of genomic instability during bladder cancer progression

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

overall_design: Refer to individual Series


title: SNP6 and expression profiling of papillary carcinoma of the breast

status: Public on Jun 20 2014

city: Pieve Emanuele

first: Charlotte

middle: K Y

last: Ng

state: MI

address: Via Rita Montalcini 4

department: Biomedical Sciences

country: Italy

institute: Humanitas University

type:
SNP genotyping by SNP array
Expression profiling by array


title: SNP6 profiling of papillary carcinoma of the breast

overall_design: Affymetrix SNP6 arrays were performed according ro manufacturer's directions on DNA extracted from 16 papillary carcinomas of the breast.

first: Salvatore

last: Piscuoglio

first: Jorge

last: Reis-Filho


title: Gene expression profile of DLL4+ and DLL4- Hemato-Endothelial Progenitors (HEPs) subpopulations

status: Public on May 01 2014

first: Veronica

last: Ayllon

address: Av Ilustracion, 114

institute: GENYO. Centre for Genomics and Oncological Research

summary: In hESCs, expression of the Notch ligand DLL4 parallels the emergence of bipotent hematoendothelial progenitors (HEPs) and promotes their hematopoietic differentiation. During differentiation, DLL4 is only expressed in a subpopulation of HEPs. To study the developmental fate of the two subpopulations of HEPs identified by DLL4 expression, we FACS-isolated DLL4high and DLL4low/- HEPs at day 15 of differentiation and performed gene expression analysis using microarrays

overall_design: 10^5 DLL4high and DLL4low/- HEPs purified by FACS from H9 and AND1 hEBs at day 15 of hematopoietic differentiation were used for gene expression analysis using Whole Human Genome Oligo Microarray chips (Agilent Technologies).

first: Pablo

last: Menendez


title: Significance of SALL4 as a drug resistant factor in lung cancer

status: Public on Apr 30 2014

city: Sapporo

first: Nozomi

last: Yanagihara

address: South-1, West-16, Chuo-Ku

department: Department of Clinical Laboratory Medicine

institute: Sapporo Medical University School of Medicine

summary: To examine the mechanism by which SALL4 regulates drug sensitivity, approximately 65,000 molecules on a microarray chip were analyzed using lung cancer cells transduced with a SALL4 vector (pCMV6-SALL4) or a control vector (pCMV6-Mock) .

overall_design: SALL4 mRNA and protein expression markedly increased after 24 hr of SALL4 vector transduction, unlike that in the cells transduced with the control vector; these cells were used for microarray analysis.

first: Daisuke

last: Kobayashi

first: Kageaki

last: Kuribayashi

first: Maki

last: Tanaka

first: Tadashi

last: Hasegawa

first: Naoki

last: Watanabe


title: Gene expression analysis of stimulated primary ASM cells [mRNA]

status: Public on May 28 2014

city: London

first: Mark

last: Perry

address: Dovehouse Street

department: Airway Disease

institute: NHLI, Imperial College London

summary: mRNA expression was determined using the Agilent-G4851A SurePrint G3 Human GE 8x60K Microarray

overall_design: Three-condition experiment, Control vs. FCS vs. Dex+FCS stim cells. Biological replicates: 4


title: Gene expression analysis of stimulated primary ASM cells


title: Affymetrix SNP array data for chronic lymphocytic leukemia samples

city: Rome

first: Monica

last: Messina

address: Via Benevento 26

department: Department of Cellular Biotechnologies and Hematology

institute: Sapienza University

summary:
Although in 80% of CLL cases that require therapy is possible to achieve a complete  remission using a combination of fludarabine, anti-CD20 in conjunction with cyclophosphamide and/or mitoxantrone, 20% of patients do not achieve disease control with this conventional approach.  The main reason of complete remission failure is chemorefractoriness to fludarabine that occurs in up to 10% of patients requiring treatment. In order to identify new molecular predictors of refractoriness as well as druggable therapeutic targets, we combined next-generation sequencing and copy number analyses.
Affymetrix SNP array analysis was performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic samples.

overall_design: Copy number analysis of Affymetrix SNP 6.0 arrays was performed for 10 FR-CLL samples and their paired normal (non-tumoral) DNA samples, processed in the same experiment and deposited (discovery set). The analysis was then extended to 29 additional FR-CLL tumoral samples and 3 Normal DNAs processed in the same experiment, including the Reference Normal DNA provided by Affymetrix (screening set).

first: M


title: A high-throughput screen to study the role of stem cells in hemangioma tumor formation

status: Public on May 31 2014

city: New York

first: Shaghayegh

last: Harbi

institute: New York University

summary: To further the development of gene expression signatures for infantile hemangioma (IH) cells, gene expression analysis was performed of different human cell samples using Agilent whole human genome oligo microarrays. The purpose of the experiments are: a) to identify the intrinsic differences between HemSc and HemDerivatives and compare HemSc and HemDerivatives genetically; b) analyze the "stemness" genes, paracrine/endocrine associated genes ("angiocrine"), and genes that regulate development, vasculogenesis and immunity; c) identify involvement of the signaling pathways at various stages of differentiation; and d) provide new perspectives on the failure of anti-vasculogenic inhibitors currently in use.

overall_design: Expression Profiles: To employ whole human genome gene expression analysis of infantile hemangioma cells by using microarray analysis followed by qPCR and microfluidic single cell analysis to: a) survey gene expression profiles and patterns between HemSc and HemDerivatives and compare HemSc and HemDerivatives genetically; Survey gene expression profiles and patterns between different populations of infantile hemangioma cells and Controls (including HemSC, Hem-Heterogeneous, HemDerivatives, BMSC, MSC, CBSC, HUVEC, and Glioblastoma CSC populations).


title: Cyclic mechanical stretch-induced gene expression

status: Public on Jun 11 2014

city: Berlin

first: Maria

last: Reichenbach

address: Thielallee 63

department: Institute for Chemistry and Biochemistry

institute: Freie Universität Berlin

summary:
With gene expression profiling it was aimed to identify the differentially expressed genes associated with the regulation of the cytoskeleton to investigate the stretch-induced cell alignment mechanism. A whole genome microarray based analysis of the stretch-induced gene expression changes was done. Gene expression was measured at the beginning of the alignment process showing first reoriented cells after 5 h stretching and at the end after 24 h, where nearly all cells are aligned.
Cyclic mechanical stretching of cells results in cellular alignment perpendicular to the stretch direction regulating cellular response. This stress response is assumed to be an adaptation mechanism to reduce extensive stretching but also acts as architectural restructuring changing performance and biomechanics of the tissue. Gene expression profiling of control vs. stretched primary human dermal fibroblasts after 5 h and 24 h demonstrated the regulation of differentially expressed genes associated with metabolism, differentiation and morphology.

overall_design: Primary human dermal fibroblasts from ten donors were cultured on Bioflex culture plates and stretched for 5h and 24 h or left untreated to avoid changes according to cell culturing. Each of the subject provided 4 samples (control/treated and 5hrs/24hrs) resulting in 40 samples total.

first: Bodo

last: Brückner

first: Hendrik

last: Reuter


title: Comparison of gene expression in radio-resistant and radio-sensitive patient-derived spheroid cultures of small cell carcinoma of the cervix

status: Public on Apr 07 2014

city: Kyoto

first: Aya

last: Nakajima

address: 54 Kawahara-cho, Shogoin, Sakyo-ku

department: Radiation Oncology

institute: Kyoto University

summary: We  established panels of patient-derived culture of the cancer cells from small cell carcinoma of the cervix uteri (SCCC) by cancer tissue–originated spheroids (CTOS) method. Then we developed in vitro sensitivity assay for radiation using CTOSs to assess the intrinsic radio-sensitivity and mechanism of radio-resistance in individual SCCC patients. To find factors that affect to the radio-sensitivity we compared gene expression of radio-resistant CTOS (cerv-5) and radio-sensitive CTOS (cerv-9).

overall_design: We compared gene expression of cerv5 and cerv9 CTOSs under the culture condition.

first: Masahiro

last: Inoue


title: Understanding molecular mechanisms of Cetuximab insensitivity in Colorectal Cancer (CRC)

status: Public on Apr 01 2014

city: Bangalore

first: Pradip

last: Majumder

address: Suite 202, Narayana Nethralaya, Narayana Hrudayalaya Health City, Hosur Main Road, Bangalore 99, Karnataka State.

country: India

institute: Mitra Biotech Pvt Ltd.

summary: Mutational status of KRAS in CRC is used to aid patient stratification for Cetuximab treatment. However, only a subset (10-40%) of patients with wt KRAS respond. We analyzed 40 mCRC tumors for Cetuximab response using a functional ex vivo platform. In the subset of non-responsive tumors, mutational (KRAS/BRAF and PIK3CA) and expression (AREG/EREG) analysis of key genes, transcriptomic profiling and GSEA were carried out to elucidate the molecular mechanisms underlying the response. Our analysis revealed deregulation of multiple pathways, notably Notch and Erbb2 and combined blockade of these two nodes elicited significant antitumor response. These findings collectively indicate the dependence of Cetuximab insensitive mCRC tumors on Notch and Erbb2 for survival and progression.

overall_design: 8 Primary tumors tested in ex vivo platform for response to Cetuximab were subjected to expression analysis

first: Nilesh

last: Brijwani


title: Polarity gene alterations in pure invasive micropapillary carcinomas of the breast

city: Paris

first: Jaydutt

middle: D

last: Bhalshankar

address: 26 rue d'Ulm

department: INSERM UNIT 830

country: France

institute: Institut CURIE

summary: In this study we  have  identified  a  new  morphological  pattern  in  IMPC  defined  by  the presence of numerous bi-nucleated cells, related to abnormal expression of genes involved in regulation of mitosis. We also demonstrated that IMPC presented tight and adherens junctions proteins expression modifications that could participate to their clinical behavior. We showed that  IMPC  was  associated  with  a  specific  genomic  profile  compared  to  ER+ grade-matched IDC consisting of gains of 17q, high rates of 17q23 and 17q12 ERBB2 amplifications, losses of  heterozygosity  of  6q.  The  putative  role  of  the  genes  located  in  this  6q  LOH  should  be further investigated in order to determine if they could play a role in the presence of numerous bi-nucleated cells and inverted polarity of IMPC cells. In addition, we identified two genomic IMPC subsets: the first characterized by numerous amplicons with frequently near-tetraploid cells  and  the  second,  associated  with  different  complex  gains  and  losses  in  addition  to  8q gains and 16q losses, and predominantly composed of near-diploïd cells. The observation of two genomic subsets within the IMPC entity suggests the existence of two possible oncogenic mechanisms leading to the development of a single disease.

overall_design: Phenotypical analysis was combined with copy number, genotyping (SNP6.0 Affymetrix) and transcriptomic analyses in a series of 39 pure IMPC. The results were compared to those of 27 ER and grade-matched invasive ductal carcinomas (IDC).

first: Nadège

last: Gruel

first: Vanessa

last: Benhamo

first: Tatiana

last: Popova

first: Aurélie

last: Cedenot

first: Odette

last: Mariani

first: Arnaud

last: Gautier

first: Ilaria

last: Cascone

first: Laurent

last: Arnould

first: Paul

last: Fréneaux

first: Franck

last: Assayag

first: Gaëlle

last: Pierron

first: Fabien

last: Reyal

first: Séverine

last: Alran

last: Cottu

first: Alain

last: Fourquet

first: Xavier

last: Sastre-Garau

first: Marc-Henri

last: Stern

first: Jacques

last: Camonis

first: Olivier

last: Delattre

first: Anne

last: Vincent-Salomon


title: Long non-coding RNA HOTAIR is expressed in small cell lung cancer and is relevant to cellular proliferation, invasiveness and clinical relapse: tissue and cell-line analyses

status: Public on Mar 05 2014

city: Tokyo

first: Hiroshi

last: Ono

address: 3-8-31 Ariake, Koto-ku

department: Pathology

institute: The Cancer Institute of JFCR

summary: LincRNA HOTAIR was expressed in pure SCLC and higher expression was significantly related to lymphatic invasion and relapse. Multivariate analyses demonstrated that HOTAIR expression correlated with RFS. In vitro experiments demonstrated that half of SCLC cell lines expressed HOTAIR at higher levels than normal cells and that, using cells of SBC-3, knockdown of HOTAIR decreased proliferative activity and cellular invasiveness with altered expression of cell adhesion-related genes.

overall_design: Total RNAs from one siHOTAIR-transfected SBC-3 cells and control cells (siGFP-transfected cells), were extracted using RNeasy mini kit Plus (Qiagen) and hybridized to the microarrays, Sure Print G3 Human GE 8x60K microarrays (Agilent Technologies, Santa Clara, CA, USA), according to the manufacturer’s instructions. Subsequently, data analysis was carried out using the GeneSpring GX 12 software (Agilent Technologies), with a stringency of P<0.1 and a 2-fold or more change using gene ontology analysis.

first: Yuichi

last: Ishukawa


title: Affymetrix SNP 6.0 array data for Diffuse Intrinsic Pontine Glioma

status: Public on Mar 31 2014

city: Toronto

first: Pawel

last: Buczkowicz

address: 686 Bay Street

department: Paediatric Laboratory Medicine

institute: Hospital for Sick Children

summary: Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal brain cancer that arises in the brainstem of children with no effective treatment and near 100% fatality. The failure of most therapies can be attributed to the delicate location of these tumors and choosing therapies based on assumptions that DIPGs are molecularly similar to adult disease. Recent studies have unraveled the unique genetic make-up of this brain cancer with nearly 80% harboring a K27M-H3.3 or K27M-H3.1 mutation. However, DIPGs are still thought of as one disease with limited understanding of the genetic drivers of these tumors. To understand what drives DIPGs we integrated whole-genome-sequencing with methylation, expression and copy-number profiling, discovering that DIPGs are three molecularly distinct subgroups (H3-K27M, Silent, MYCN) and uncovering a novel recurrent activating mutation in the activin receptor ACVR1, in 20% of DIPGs. Mutations in ACVR1 were constitutively activating, leading to SMAD phosphorylation and increased expression of downstream activin signaling targets ID1 and ID2. Our results highlight distinct molecular subgroups and novel therapeutic targets for this incurable pediatric cancer.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from snap frozen biopsy and autopsy brain tissue from DIPG patients.
Copy number analysis on Affymetrix 6.0 SNP arrays was performed for 45 paediatric DIPG samples, 27 matched normal brain samples, and HapMap samples.

first: Christine

last: Hoeman

first: Patricia

last: Rakopoulos

first: Sanja

last: Pajovic

first: Louis

last: Letourneau

first: Misko

last: Dzamba

first: Andrew

last: Morrison

first: Peter

last: Lewis

first: Eric

last: Bouffet

first: Ute

last: Bartels

first: Jennifer

last: Zuccaro

first: Sameer

last: Agnihotri

first: Scott

last: Ryall

first: Mark

last: Barszczyk

first: Yevgen

last: Chornenkyy

first: Mathieu

last: Bourgey

first: Guillaume

last: Bourque

first: Alexandre

last: Montpetit

first: Francisco

last: Cordero

first: Pedro

last: Castelo-Branco

first: Joshua

last: Mangerel

first: Uri

last: Tabori

first: Polly

middle: C

last: Ho

first: Annie

last: Huang

first: Kathryn

last: Taylor

first: Alan

last: Mackay

last: Bendel

first: Javad

last: Nazarian

first: Jason

middle: R

last: Fangusaro

first: Matthias

last: Karajannis

first: David

last: Zagzag

first: Nicholas

last: Foreman

last: Donson

first: Julia

middle: V

last: Hegert

first: Amy

last: Smith

last: Chan

first: Lucy

last: Lafay-Cousin

first: Sandra

last: Dunn

first: Juliette

last: Hukin

first: Chris

last: Dunham

first: Katrin

last: Scheinemann

first: Jean

last: Michaud

first: Shayna

last: Zelcer


title: Th17, Th22 and Treg cells are enriched in the healthy human cecum

status: Public on Feb 22 2014

city: Saint Louis

first: Mei San

last: Tang

state: MO

address: 660 S Euclid, Campus Box 8118

department: Pathology & Immunology

institute: Washington University in St Louis

summary: Dysregulation of CD4+ T cell populations leads to intestinal inflammation, but the regional differences of these T cell populations remained unclear in the healthy population. We first used flow cytometry to show that Th17 and Th22 cells are specifically enriched in the human cecum, while Th1 and Th2 cells do not differ regionally. We subsequently performed transcriptional profiling and found that Th17 was positively associated with the expression of RETN and negatively associated with TFF1, suggesting that the differential enrichment of Th17 cells in the healthy human cecum was underlined by the metabolic differences in this environment.

overall_design: Transcriptional profiling with microarray on human intestinal pinch biopsies obtained from different sites of the healthy colon.

first: Martin

last: Wolff

first: Jacqueline

last: Leung

first: Michael

last: Davenport

middle: A

last: Poles

first: Ilseung

last: Cho

first: P'ng

last: Loke


title: Oncogene-like induction of cellular invasion from centrosome amplification

status: Public on Mar 01 2014

first: Susana

last: Godinho

state: State...

address: Charterhouse Square

department: Centre for Molecular Oncology

institute: Barts Cancer Institute

summary: Centrosome amplification has long been recognized as a feature of human tumors, however its role in tumorigenesis remains unclear. Centrosome amplification is poorly tolerated by non-transformed cells, and, in the absence of selection, extra centrosomes are spontaneously lost. Thus, the high frequency of centrosome amplification, particularly in more aggressive tumors, raises the possibility that extra centrosomes could, in some contexts, confer advantageous characteristics that promote tumor progression. Using a three-dimensional model system and other approaches to culture human mammary epithelial cells, we find that centrosome amplification triggers cell invasion. This invasive behavior is similar to that induced by overexpression of the breast cancer oncogene ErbB2 and indeed enhances invasiveness triggered by ErbB2.  We show that, through increased centrosomal microtubule nucleation, centrosome amplification increases Rac1 activity, which disrupts normal cell-cell adhesion and promotes invasion. These findings demonstrate that centrosome amplification, a structural alteration of the cytoskeleton, can promote features of malignant transformation.

overall_design: genome-wide human SNP 6.0 arrays from Affymetrix was used to determine the copy number changes of MCF10A cells with extra centrosomes or depleted of MCAK after grown 4 days in 3-D cultures

first: David

last: Pellman


title: Diffuse Intrinsic Pontine Glioma

first: Pawel

last: Buczkowicz

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


title: Human colon carcinoma cell line treated with bafilomycin A1

status: Public on Feb 19 2014

city: Martinsried

first: Milena

last: Dürrbaum

address: Am Klopferspitz 18

department: Maintenance of Genome Stability

institute: Max Planck Institute of Biochemistry

summary: Analysis of mRNA expression changes in human colon carcinoma cell lines (HCT116 H2B-GFP) after treatment bafilomycin A1.

overall_design: mRNA expression analysis of HCT116 H2B-GFP treated with bafilomycin A1 compared to untreated HCT116 H2B-GFP. Four biological replicates were performed for treated samples.

first: Silvia

last: Stingele

first: Gabriele

last: Stoehr

first: Zuzana

last: Storchová


title: Blood expression profiles of fragile X premutation carriers identify genes involved in neurodegenerative and infertility phenotypes [FXTAS]

status: Public on Feb 20 2014

city: Barcelona

first: Elisabet

last: Mateu Huertas

state: Barcelona

address: Dr. Aiguader, 88

department: Bioinformatics and Genomics

institute: Center for Genomic Regulation

summary: Fragile X premutation carriers (fXPC) of the CGG expansion in the 5’-UTR of the fragile X mental retardation 1 (FMR1) gene are at high risk of Fragile X Tremor/Ataxia Syndrome (FXTAS), and females might undergo Premature Ovarian Failure (POF1). We have evaluated the peripheral blood gene expression profiles of fXPC and detected a strong deregulation of genes enriched in FXTAS-relevant biological pathways, including inflammation, and neuronal homeostasis and survival. More than 30% of differentially expressed correspond to long non-coding RNAs (lncRNAs). Several deregulated genes (CASP3, DFFA, APP, AKT1, COX6C, COX7B, SOD1, RNF10, HDAC5, ATXN7, ATXN3 and EAP1) were validated in brain samples of a mouse model of FXTAS and in neuronal cells expressing the expanded FMR1 5’-UTR. One of the validated genes is the early at menopause 1 (EAP1) gene. We confirmed the EAP1 deregulation both in male and female fXPC. Down-regulation was stronger in female fXPC with POF1 compared with female fXPC without POF1. Increased levels of FMR1 mRNA were detected in all brain areas of the CGG-KI mouse model. EAP1 was significantly downregulated in the brainstem and cerebellum of the KI mouse, suggesting that EAP1 levels in certain brain areas could contribute to POF in this model. All together, these results suggest that gene expression profiling in blood of fXPC reflects changes in the brain transcriptome that may underlie neuropathological aspects in FXTAS and of POF.

overall_design: In the study presented here, we have 5 control samples plus one biological replicate and 9 patients with CGG expansions in the 5'UTR of the FMR1 gene (being premutation carriers)

last: Mateu-Huertas

first: Laia

last: Rodriguez-Revenga

first: Maria

last: Alvarez-Mora

first: Rob

last: Willemsen

first: Montserrat

last: Milá

first: Eulàlia

last: Martí

first: Xavier

last: Estivill


title: Uniform response to aneuploidy in human cells

summary: There are many different types and origins of aneuploidy, but whether there is a uniform cellular response to aneuploidy in human cells has not been addressed so far. To uncover a uniform transcriptional response to aneuploidy we evaluted the transcription profiles of trisomic and tetrasomic cell lines and cell lines with complex aneuploid karyotypes.

overall_design: mRNA expression analysis of aneuploid cell lines derived from HCT116 compared to the HCT116 diploid cell line. With the exception of HCT116 3/3, three biological replicates of the Microarray experiment were performed.

first: Anastasia

last: Kuznetsova

first: Verena

last: Passerini


title: Blood expression profiles of fragile X premutation carriers identify genes involved in neurodegenerative and infertility phenotypes

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

overall_design: Refer to individual Series


title: Respective Prognostic Value of Genomic Grade and Histological Proliferation Markers in Early Stage (pN0) Breast Carcinoma

status: Public on Feb 18 2014

first: Jaydutt

last: Bhalshankar

summary: Phenotypic and genomic characterization of  Early Stage Breast Carcinoma using Training set (n=109) Validation set (n=105) of SNP6 arrays

overall_design: Affymetrix SNP6.0 arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved breast tumoral samples.

first: Fabien

last: Reyal

first: Marc

last: Bollet

first: Martial

last: Caly

last: Gentien

first: Sabrina

last: Carpentier

first: Helene

last: Peyro-Saint-Paul

first: Jean-Yves

last: Pierga

first: Paul

last: Cottu

first: Veronique

last: Dieras

first: Brigitte

last: Sigal-Zafrani

first: Anne

last: Vincent-Salomon

last: Sastre-Garau


title: mRNA Expression Profiling in EBV-postive Gastric Carcinoma and EBV-negative GC in comparison with their normal mucosa tissue

city: Goyaongsi

first: Charny

last: Park

state: Gyeonggi-do

address: 323 Ilsan-ro,

institute: National Cancer Center

summary: The better prognosis of patients with Epstein-Barr virus-positive gastric carcinoma than those with EBV-negative GC is correlated with the degree of recruitment of inflammatory tumor infiltrating cells (TIL) to the vicinity of tumor cells. We hypothesized that the better prognosis would associate with less genetic or epigenetic alterations in EBV(+)GC, or EBV infection should deregulate immune modulator proteins, of which secretion recruit TIL. Therefore we performed mRNA expression profilings in EBV(-)GC and EBV(+)GC, each of which was pair wise compared with their normal control. We found that EBV(+)GC had much more molecular homogeneity with focused alterations in immune modulator genes; The Pearson correlation matrix analyses demonstrated that EBV(+)GC tumor showed remarkably high tumor homogeneity. While EBV(-)GC had considerable number genes that are differentially expressed genes from their normal counterparts, EBV(+)GC showed only a handful, almost 20 fold less number of DEG than EBV(-)GC under the same p value cutoff (p<0.001). Gene ontology and pathway analyses showed that while pathways of cation homeostasis, digestion and ion transport were commonly deregulated in both GC types, genes for chromatin assembly, prostaglandin receptor activity, pattern specification process are selectively deregulated in EBV(-)GC tumors. In contrast, pathways or genes for cytokine activity, immune response and lipoprotein particle clearance are selectively deregulated in EBV(+)GC tumors. These results demonstrate that EBV(+)GC inherently evolves to high homogeneity with fewer changes in gene expression and these secret immune modulatory chemokines could recruit reactive immune cells to EBV(+)GC, leading to favorable microenvironment for cancer suppression.

overall_design: All patients underwent the surgery for advanced gastric carcinoma (GC) except one patient with early GC. The EBV-presence in the GC was verified by in situ EBV-encoded small RNA (ERER) staining.. The 14 paired EBV(-)GC patients and 12 paired EBV(+)GC patients were selected for this study. Tumor tissue (T)and normal tissues (N) from distant sites from tumor areas were dissected, frozen at -80C and were subjected to RNA purification, mRNA array profiling analyses.

first: Myung-Soo

last: Kang

first: Sun

last: Kim

first: Ha-Jung

first: Kyoung

first: Sung

first: Minkyu

last: Choi

first: Kyung-A

last: Song

first: Eun

middle: K

last: Lee


title: Identification of target genes regulated by ΔNp63α in SaOS-2 cells stably expressed with ΔNp63α

status: Public on Feb 27 2014

city: Zurich

first: Ram Mohan

last: Ram Kumar

address: Forchstrasse 340

department: Orthopaedics

institute: University Hospital Balgrist, University of Zurich, Zurich, Switzerland

summary: To identify the target gene of ΔNp63α, in osteosarcoma cells, we performed the global gene expression profiling in SaOS- 2 cells stably overexpressing the ΔNp63α gene (SaOS- 2-ΔNp63α). ΔNp63α target genes were identified by comparison  with genes expressed from  SaOS-2-EV  transfected with an empty vector ( SaOS-2-EV).

overall_design: Total RNA was extracted from  SaOS- 2-ΔNp63α and SaOS-2-EV cells  cultured in  three independent replicates for each condition. Cy3-labeled cRNA was synthesized and hybridized to  Agilent  human 8 x 60K   microarrays. Raw data, obtained after array image analysis were normalized and used to retrieve differentially expressed genes in ΔNp63α overexpressing SaOS- 2 cells and genes from control SaOS-2-EV cells.

first: Ram

first: Born

last: Walter

first: Maria

last: Lecca

first: Bruno

last: Fuchs


title: Gene expression from pericytes and endothelial cells

status: Public on Jan 01 2014

city: Vienna

first: Klemens

last: Vierlinger

address: Giefinggasse 4

department: HMD

country: Austria

institute: AIT

summary: Aims: Vascular wall resident stem cells (SCs) hold great promise for cardiovascular regenerative therapy. This study evaluated the impact of oxidative stress on the viability and functionality of saphenous vein'derived pericytes (SVPs), SVPs'deriv ed cells and terminally differentiated vascular cells. We also investigated the molecular mechanisms underlying the SVP resistance to oxidative stress. Results: SVPs exhibit a significantly higher resistance to oxidative stress resulting in reduced apoptosis upon exposure to hydrogen peroxide in comparison to endothelial cells (ECs). This was attributed to upregulation of genes encoding for anti'oxidant enzymes, especially superoxide dismutases (SODs) and catalase. Pharmacological inhibition of SODs increased ROS levels in SVPs and impaired their survival. Furthermore, we confirm that, when exposed to differentiation stimuli, SVPs are able to generate mesodermic lineages. Interestingly, differentiation of SVPs resulted in SOD down'regulation and increased apoptosis upon exposure to hydrogen peroxide. Oxidative stress caused an incremental increase on SVPs migration, whilst being inhibitory for the ECs. Additionally, oxidative stress did not impair SVPs capacity to promote angiogenesis in vitro. Innovations: This study for the first time demonstrates that SCs resident in veins of cardiovascular patients are endowed with enhanced detoxifier and antioxidant system. Conclusions: SVPs expanded from vein remnants of coronary artery bypass graft surgery express antioxidant defense mechanisms which allow them resist to high levels of ROS. These properties highlight the potential of SVPs in cardiovascular regenerative medicine.

overall_design: 2 groups 3 replicates

first: Iacobazzi

last: Dominga

first: Gubernator

last: Moriam

first: Mangialardi

last: Giuseppe

first: Hofner

last: Manuela

first: Wielsher

last: Matthias

first: Vierlinger

last: Klemens

first: Montagnani

last: Monica

first: Madeddu

last: Paolo


title: A recurrent 11q aberration pattern characterizes a subset of MYC-negative mature aggressive B-cell lymphomas resembling Burkitt lymphoma

status: Public on Jan 10 2014

first: Itziar

last: Salaverria

address: Rossello 153

institute: Hospital Clínic


title: Affymetrix SNP array data for 4 MYC-negative B-cell lymphoma cases and 2 B-cell lymphoma cell lines (SU-DHL-5 and HT)

summary: Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from blood samples and cell lines

overall_design: Copy number analysis of Affymetrix SNP 6.0 arrays was performed for 4 MYC-negative B-cell lymphoma and 2 B-cell lymphoma cell lines

first: Reiner

last: Siebert


title: miR-34 regulates JARID1A expresion (NB1691)

city: Memphis

first: JUN

last: YANG

state: TN

address: 262 Danny Thomas Place

department: Surgery

institute: St Jude Children's Research Hospital

summary: p53 inactivation occurs only rarely in neuroblastoma, although miR-34, a transcriptional target of p53, is often deleted in neuroblastoma, suggesting  another way in which p53 signaling might be impaired. In this study we show that miR-34 directly targets and downregulates the Polycomb Repressive Complex 2 (PRC2) and its associated histone demethylase, JARID1A, in a p53-dependent manner,

overall_design: 8 samples were transfected with siRNA control or JMJD2B, MYCN, JARID1A into NB1691 cells.

first: Jun

last: Yang

first: Andrew

last: Davidoff


title: Paternal segmental isodisomy of centromeric region on chromosome 1 as a cause of juvenile hemochromatosis

status: Public on Jan 30 2014

city: Prague

first: Viktor

last: Stranecky

address: Ke Karlovu 2

department: 1st Faculty of Medicine

country: Czech Republic

institute: Charles University

summary:
Juvenile hemochromatosis type 2A in the studied patient was caused by a homozygous mutation c.196G>T (p.G66*) in hemojuvelin.
Homozygous state for this mutation evolved through interstitial segmental isodisomy encompassing the centromeric region of chromosome 1 accompanying its paternal disomy.
The disomy resulted into normal karyotype

overall_design: SNP genotyping was performed on 3 samples - family trio. Affymetrix GeneChip Command Console software was used for image processing and CEL files were processed by Affymetrix GTC using the BRLMM-P-Plus algorithm and regional GC correction configuration for Copy Number/LOH analysis. The HapMap270 file supplied by Affymetrix was used as the reference.

first: Magdaléna

last: Neřoldová

first: Milan

last: Jirsa


title: Gene expression of T47D-MTVL human breast cancer cells growing in normal conditions

status: Public on Feb 04 2014

first: Albert

last: Jordan

address: Baldiri Reixac 4

department: Molecular Genomics

institute: IBMB-CSIC

summary: Basal gene expression of T47D-MTVL human breast cancer cells growing in normal conditions

overall_design: Breast cancer cells T47D-MTVL cells were grown in rich media and total RNA was extracted to monitor basal gene expression

first: Lluís

last: Millán-Ariño


title: CD7 promotes extramedullary involvement of the B-cell acute lymphoblastic leukemia line Tanoue by enhancing integrin beta2-dependent cell adhesiveness

status: Public on Dec 27 2013

city: Sapporo

first: takashi

last: kondo

state: Hokkaido

address: South-1, West-16, Chuo-ku

department: Clinical Laboratory Medicine

institute: Sapporo Medical University

summary: The Tanoue expressing firefly-luciferase gene, Luc-Tanoue, was transplanted into non-obese diabetic/severe combined immunodeficient mice, and cells infiltrated in the brain were cultured ex vivo. This process was repeated 4 times to obtain the highly invasive line Luc-Tanoue-F4. Comparison of the global gene expression signatures of Luc-Tanoue-F4 and Luc-Tanoue indicated that the CD7 gene showed the largest increase in expression among EMI-related genes in Luc-Tanoue-F4.

first: Takashi

last: Kondoh

first: Kageaki

last: Kuribayashi

first: Maki

last: Tanaka

first: Naoki

last: Watanabe


title: Affymetrix SNP6 array data for ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH) samples

status: Public on Nov 28 2013

city: PARIS

first: Guillaume

last: Assié

address: 24 rue du Fg Saint Jacques

department: Endocrinology Metabolism Cancer

institute: Institut Cochin

summary:
AIMAH is an ACTH-independent bilateral enlargement of the adrenal cortex occuring during adulthood. The enlargment is related to the growth of multiple benign nodules. This condition is associated with various degrees of cortisol hypersecretion. The occurence of several nodules in both adrenals, and the existence of familial forms, suggest the existence of a germline genetic predisposition. To find the gene(s), the aim of the project was to look for recurrent chromosomal alterations in the AIMAH nodules. Extensive mapping of somatic gains, losses and copy-neutral loss of heterozygosity (LOH) was performed with Affymetrix SNP6 arrays. A copy neutral LOH of 16p, occuring in 7 of 26 patients, was one of the only recurrent alterations, pointing towards a candidate gene in this region. Of note this condition differs from the congenital adrenal hyperplasias, related to genetic alterations of steroidogenesis (the latter is an ACTH dependent adrenal hyperplasia).
Affymetrix SNP6 arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved tumor samples or peripheral blood samples.

overall_design: Copy number and LOH analysis of Affymetrix SNP6 arrays was performed for AIMAH nodules from 26 patients, including 18 with paired leucocyte and nodules (1 to 4 nodules per patient), and 8 with a single nodule (no paired leucocyte available)

first: Rossella

last: Libé

first: Windy

last: Luscap

first: Bruno

last: Ragazzon

first: Jérôme

last: Bertherat


title: Affymetrix SNP6.0 array data for different clinical outcomes of HBV infection

status: Public on Dec 10 2013

city: Wuhan

first: Lin

last: Ju-Sheng

state: Hubei

address: 1095 Jiefang Road

department: Gastroenterology

country: China

institute: Tongji Hospital

summary: Chronic hepatitis B virus (HBV) infection is a serious global public health problem. To identify susceptibility loci for disease progression of HBV infection, we performed this genome-wide association study using DNA pools of case and control constructed by progressed HBV carriers (acute liver failure, liver cirrhosis, hepatocellular carcinoma) and asymptomatic HBV carriers separately. Performing GWAS on pools of DNA samples is an effective strategy to reduce the costs of studies and pooling DNA has been shown to be an efficient method to select candidate susceptibility loci for follow-up by individual genotyping.

overall_design: Affymetrix Genome-Wide Human Mapping SNP6.0 Arrays were performed for DNA pools, which were constructed by pooling 120 ng DNA from each participant. Four independent pools were created: case A was acute liver failure group (n = 86), case B was liver cirrhosis group (n = 88), case C was hepatocellular carcinoma group (n = 90) and case D was asymptomatic HBV carriers (n = 66) that was considered as control. Twelve chips (each pool was replicated in triplicate) were finished according to the manufacturer's instruction.

first: Li-Feng

last: Liu

first: Ju-Sheng

last: Lin

first: Jin-Jian

last: Yao

first: Jin

last: Li

first: Xing-Xing

last: He

first: Ying

last: Chang


title: Function of chemokine (CXC motif) ligand 12 in periodontal ligament fibroblasts

status: Public on Nov 07 2013

city: yokohama-shi

first: yuichi

last: yashiro

state: kanagawa

department: orthodontic department

country: Japan

institute: tsurumi university

summary: The periodontal ligament (PDL) is one of the connective tissues located between the tooth and bone. It is characterized by rapid turnover. Periodontal ligament fibroblasts (PDLFs) play major roles in the rapid turnover of the PDL. Microarray analysis of human PDLFs (HPDLFs) and human dermal fibroblasts (HDFs) revealed markedly high expression of chemokine (CXC motif) ligand 12 (CXCL12) in the HPDLFs, which plays an important role in the migration of mesenchymal stem cells (MSCs). The function of CXCL12 in the periodontal ligament was investigated in HPDLFs. CXCL12 in HPDLFs and HDFs was examined by microarray, RT-PCR, qRT-PCR and ELISA. It was also immunohistochemically examined in the PDL in vivo. Chemotactic ability of CXCL12 was evaluated both in PDLFs and HDFs with migration assay of MSCs. The expression of CXCL12 in the HPDLFs was much higher than that in HDFs in vitro. CXCL12 was localized in fibroblasts and extracellular matrix in the PDL in rats. Migration assay demonstrated that the number of migrated MSCs by HPDLFs was significantly higher than that by HDFs. In addition, the migrated MSCs also expressed CXCL12 and several genes that are familiar to fibroblasts. The results suggested that PDLFs are able to synthesize and secrete CXCL12 protein, and that CXCL12 induces migration of MSCs in the PDL in order to maintain rapid turnover of the PDL.

overall_design: The objective of this study was to investigate the function of CXCL12 in the PDL with rapid turnover.Microarray analysis was performed using a Whole Human Genome 8x60K (Agilent Technologies, Tokyo, Japan) containing approximately 44,000 transcripts. According to the manufacturer’s protocol, total RNAs from HPDLFs and HDFs were labeled with Cy3 and hybridized on the microarray. The hybridization data for HPDLFs were compared with data for HDFs.

first: Yuichi

last: Yashiro

first: Yoshiaki

last: Nomura


title: Distinct Mutational Patterns of Infection and Non-Infection-Related Bile Duct Cancers Revealed by Exome Sequencing

status: Public on Nov 03 2013

city: Singapore

first: Ioana

last: Cutcutache

state: Singapore

address: 8 College Rd

department: Centre for Computational Biology

country: Singapore

institute: Duke-NUS

summary: The impact of different carcinogenic exposures on the specific patterns of somatic mutations in human tumors remains unclear. To clarify this issue, we profiled 209 cholangiocarcinomas (CCAs) from Asia and Europe, including 108 cases caused by liver fluke Opisthorchis viverrini (OV)-infection and 101 cases due to non-OV etiologies. Whole-exome (N = 15) and prevalence screening (N = 194) revealed recurrent somatic mutations in BAP1 and ARID1A, neither of which has been previously reported to be mutated in CCA. Comparisons between intrahepatic OV and non-OV CCAs demonstrated statistically significant different mutation patterns: BAP1 and IDH1/2 were more frequently mutated in non-OV CCAs, while TP53 displayed the reciprocal pattern. Functional studies demonstrated tumor suppressive roles of BAP1 and ARID1A, establishing the role of chromatin modulators in CCA pathogenesis. These findings indicate that different causative etiologies may induce distinct somatic alterations even within the same tumor type.

overall_design: Affymetrix SNP6 arrays were performed according to the manufacturer's directions on DNA extracted from the 15 tumors and the 15 matched normal discovery samples.

first: Waraporn

last: Chan-on

first: Bin

middle: T

last: Teh


title: Effect of aryl hydrocarbon receptor (Ahr) gene knockout on expression profiles of murine hematopoietic stem cells

status: Public on Nov 08 2013

city: Rochester

first: Stephen

last: Welle

state: NY

address: 601 Elmwood Avenue

country: USA

institute: University of Rochester

summary: As part of a study of the role of the aryl hydrocarbon receptor (Ahr) in maintenance and senescence of hematopoietic stem cells (HSC), global gene expression profiling was done with HSC isolated from  Ahr-knockout and wild-type mice. HSC from young-adult (8 wk old) AhR-KO mice had changes in expression of many genes related to HSC maintenance, consistent with the phenotype observed in aging Ahr-KO mice: decreased survival rate, splenomegaly, increased circulating white blood cells, hematopoietic cell accumulation in tissues, anemia,  increased numbers of stem/progenitor and lineage-committed cells in bone marrow, decreased erythroid progenitor cells in bone marrow, and decreased self-renewal capacity of HSC.

overall_design: 7 samples: 3 Ahr knockout, 4 wild-type

first: Kameshwar

last: Singh

first: Thomas

last: Gasiewicz


title: CD8+ T cell gene expression after different antigen dose stimulations

status: Public on Dec 01 2013

city: Baltimore

first: Yen-Ling

last: Chiu

state: MD

address: 733 N. Broadway, BRB 615

institute: Johns Hopkins University

summary: This study aimed to identify the human T cell response toward different antigen doses. Fresh isolated CD8+ T cells from peripheral blood mononuclear cells (PBMCs) were stimulated with influenza M1 peptide-loaded autologous monocyte-derived dendritic cells for 2 weeks. A high M1 peptide antigen dose (10uM on moDC, HD1-5) and an optimal antigen dose (10nM on moDC OD1-5) were used. M1-specific CD8 T cells were tetramer sorted at the end of the 2 weeks. RNA was extracted and analyzed for gene expression using Agilent 8X60K gene expression microarrays.

overall_design: 5 independent samples from 3 different HLA A2+ blood donors.

first: Yen

middle: L

first: Jonathan

last: Schneck


title: Human whole blood microarray study to compare patients with tuberculosis, sarcoidosis, pneumonia, and lung cancer

status: Public on Oct 31 2013

city: London

first: Chloe

last: Bloom

address: The Ridgeway

country: United Kingdom

institute: MRC National Institute for Medical Research

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

[Third party comment]  Samples with identical non-normalized expression values are identified at: https://colab.research.google.com/drive/1swvQGf-ZLAWnZw-7bOCmsypzzAnCDGUR#scrollTo=mIqv_oTHc6ns


title: Affymetrix SNP array data for follicular lymphoma (FL) and transformed follicular lymphoma (tFL) samples

status: Public on Oct 01 2013

first: Jun

last: Wang

address: Charterhouse Square

institute: Barts Cancer Institute, Queen Mary, London

summary: Follicular lymphoma is the most common indolent non-Hodgkin's lymphoma involving germinal centre B cells, with a subset of patients undergoing transformation to a diffuse large B-cell lymphoma (DLBCL) morphology for which the clinical outcomes are poor. To elucidate the differences in copy number profiles between FL and tFL groups, we performed Affymetrix SNP 6.0 Array analysis on 31 paired FL-tFL cases. We wanted to identify and compare recurrent somatic copy number alterations (CNAs) between the two groups (FL vs. tFL). In addition, the concordance and discordance in the copy neutral loss of heterozygosity (cnLOH) between the two groups were also investigated to identify recurrent target gene regions.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from follicular lymphoma (FL), transformed follicular lymphoma (tFL) and matching germline (GL) sample (if available).
Copy number analysis of Affymetrix SNP 6.0 Array were performed on 91 DNA samples, consisting of 31 patients. Among the 31 patients, 19 had matching germline samples, while 12 had no germline samples. The Log R Ratio (LRR) values and the B Allele Frequency (BAF) values were subsequently calculated to search for copy number aberrations and copy neutral (CN)-LOH in the FL and tFL samples. Paired and unpaired analyses were performed accordingly.

first: Jessica

last: Okosun

first: Csaba

last: Bodor

first: Jude

last: Fitzgibbon


title: Affymetrix SNP 6.0 data for analysis of esophageal adenocarcinoma samples

city: Pittsburgh

first: William

middle: Armand

last: LaFramboise

state: PA

address: 5230 Centre Avenue

institute: University of Pittsburgh

summary: Esophageal adenocarcinoma is characterized by complex chromosomal alterations. Tumors were evaluated to identify regions of recurrent copy gains and losses and to determine the prognositic significance of the degree of segmental aneuploidy as measured by SNP array.

overall_design: 41 superficial esophageal adenocarcinomas were analyzed for copy number abnormalities. Matched normal lymph node tissue was used as a copy number reference.

first: Jon

last: Davison


title: The gene expression on human hair root

city: Tsukuba

first: Masaya

last: Seki

state: Ibaraki

address: Sengen 2-1-1

department: JEM Utilization Center

institute: Japan Aerospace Exploration agency

summary: In HAIR experiment of astronauts, the hair samples are limited to only five strands from each astronaut.  Therefore, it is essential to develop the method to analyze no less than five hair roots.  To achieve this purpose, in this study, we performed the microarray analyses using the extracted RNA from one, five, or ten hair roots.

overall_design: 13 samples from two healthy subjects

first: Masahiro

last: Terada


title: Affymetrix SNP array data for acute lymphoblastic leukemia samples

status: Public on Sep 17 2013

city: Hamburg

last: Streichert

address: Martinistr. 52, Campus Forschung N27, 2. OG

department: Institute For Clinical Chemistry / Central Laboratories

institute: University Medical Center Hamburg-Eppendorf

summary: Development of B-acute lymphoblastic leukemia accompanies with multiple variable mutations. Beside the structural and chromosomal alterations, especially mutations in the regulators of B cell differentiation are common. Around 60% of the B-ALL show deletions of these genes.

overall_design: Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. Copy number analysis of Affymetrix SNP 6.0 arrays was performed for 20 pediatric B-ALL samples and intraindividually matching remission samples which were used as references.

first: Lena

last: Harder

first: Martin

last: Horstmann

first: Benjamin

last: Otto


title: Irradiation of human and mouse placental cells

status: Public on Aug 16 2013

city: PITTSBURGH

first: Yoel

last: Sadovsky

state: Pennsylvania

address: 204 Craft Ave

department: Obstetrics and Gynecology

institute: MAGEE WOMENS RESEARCH INSTITUTE

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

overall_design: Refer to individual Series


title: Primary term human trophoblasts exposed to ionizing irradiation

summary: Primary term human trophoblasts were derived from placentas after a healthy pregnancy, and exposed to ionizing irradiation (vs sham) in vitro

overall_design: Primary human trophoblasts were irradiated 24 h after initial plating, defined as time zero. Cells were irradiated at 10 Gy using a Clinac 600C (Varian Medical Systems, Palo Alto, CA) with a 6 MV photon beam and a dose rate of 250 cGy/min. The flasks containing the cells were placed on 1.5 cm of bolus (a tissue equivalent material) since the maximum irradiation depth was 1.5 cm, which corresponded to the plated cell layer. Cells were analyzed 4, 8, and 24 h after irradiation or sham.


title: Affymetrix SNP array data for various human ES cell lines

status: Public on Dec 19 2013

city: Stockholm

first: Sergey

last: Rodin

address: Scheelesvag 2, Plan 4:B1

country: Sweden

institute: Karolinska institute

summary:
Human pluripotent stem cells commonly undergo adaptive changes during prolonged passaging in vitro. We have developed a new laminin-521 based method for self-renewal of human pluripotent stem cells.
SNP6.0 array was used to assess genetic stability of several human ES cell lines cultured in the new system with two lines (H1 and HS401) cultured on feeders (standard conditions)

Two main objectives in this study:

To compare the number of the CNVs in human ES cells at early and late passages; for example, samples HS980 p6 and HS980 p31 represent HS980 cells at passages 6 and 31, respectively. The overall conclusion is that the observed number of CNVs is similar in the cells at early and late passages. This analysis can be remade without the reference samples.

To compare the number of CNVs in control human ES  cells (H1 and HS401) grown under standard protocol with that in cells (HS980, HS983a, HS999, HS916, and HS1001) grown under a new, developed by us, protocol. Because the cells were from different individuals, we could not compare them directly. Instead, we compared them to a set of samples from 75 healthy individuals, and then with each other. For the Reference  These samples had been hybridized in the same lab as our samples, but for a different project; and the data were kindly provided by Prof. Kere. However, the same overall conclusion would result from an other sufficiently large dataset of healthy human individuals.

Please note that 75 healthy individual samples had been hybridized in the same lab as our samples and the data were kindly provided by Prof. Kere, which is linked as a Series supplementary file ('75_samples_ref.REF'). It is a Reference Model File that Affymetrix Genotyping Console software has created based on data from 75 healthy individuals (i.e. processed file based on the CEL files of the 75 healthy individuals). The file derives from the "CN/LOH Reference Model File Creation and Analysis (Batch Sample Mode)" process according to the Genotyping Console manual. It contains SNP-wise information on the observed distribution of hybridization intensities of a set of samples that are assumed to be diploid in copy number (for most part of their genomes at least). This file is then used to compare the intensities observed in the CEL files of interest to infer deviations from the reference as CNVs. Thus, in combination with the CEL files (from each ES cell line), this file enables the exact replication of the CNV analyses done for the various human ES cell lines study.

overall_design: Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted cultured human ES cells. Several lines were analysed at different time points of the experiment. The analysis was done using default parameters and comparing each sample against a reference set of 75 healthy individuals provided by Juha Kere.

first: Karl

last: Tryggvason

first: Juha

last: Kere

first: Elina

last: Salmela


title: Affymetrix SNP6 copy number data on ovarian cancer cell lines

status: Public on Aug 01 2013

city: Vancouver

first: Michael

last: Anglesio

state: BC

country: Canada

institute: University of British Columbia

summary:
Background: Ovarian carcinomas consist of at least five distinct diseases: high-grade serous, low-grade serous, clear cell, endometrioid, and mucinous. Biomarker and molecular characterization may represent a more biologically relevant basis for grouping and treating this family of tumors, rather than site of origin. Molecular characteristics have become the new standard for clinical pathology, however development of tailored type-specific therapies is hampered by a failure of basic research to recognize that model systems used to study these diseases must also be stratified. Unrelated model systems do offer value for study of biochemical processes but specific cellular context needs to be applied to assess relevant therapeutic strategies.
Methods: We have focused on the identification of clear cell carcinoma cell line models. A panel of 32 “ovarian cancer” cell lines has been classified into histological types using a combination of mutation profiles, IHC mutation-surrogates, and a validated immunohistochemical model. All cell lines were identity verified using STR analysis.
Results: Many described ovarian clear cell lines have characteristic mutations (including ARID1A and PIK3CA) and an overall molecular/immuno-profile typical of primary tumors. Mutations in TP53 were present in the majority of high-grade serous cell lines. Advanced genomic analysis of bona-fide clear cell carcinoma cell lines also support copy number changes in typical biomarkers such at MET and HNF1B and a lack of any recurrent expressed re-arrangements.
Conclusions: As with primary ovarian tumors, mutation status of cancer genes like ARID1A and TP53 and a general immuno-profile serve well for establishing histological type of ovarian cancer cell We describe specific biomarkers and molecular features to re-classify generic “ovarian carcinoma” cell lines into type specific categories. Our data supports the use of prototype clear cell lines, such as TOV21G and JHOC-5, and questions the use of SKOV3 and A2780 as models of high-grade serous carcinoma.

overall_design:
The DNA copy number of 10 ovarian cancer cell lines was examined and changes in copy number of genes whose expression is assumed to be critical to the phenotype of ovarian clear cell carcinoma was evaluated.
Copy number data was estimated from signal intensity on Affmetrix SNP 6.0 arrays. Copy number ratio values were generated in Partek Genomics Suite (v 6.6) using a Partek corporation distributed baseline file of normal (2N) genomic DNA and default parameters. Post import values were corrected for localized GC content using the inbuilt Partek feature based on methods described in Diskin et al. (Nucleic Acids Research. 2008. 36:19).
The characteristic "literature reported histotype" is the reported histological subtype for each cell line from the originating laboratory or cell bank (repository). The characteristic "Predicted histology" is based on parameters described in Anglesio et al. (PLOS ONE 2013. in press), including immunohistochemical phenotype, presence of typical mutations, consistency in growth characteristics, and DNA copy number.  All cell lines were grown under recomended conditions, collected near confluence (80%) and not subjected to any experimental treatments or modifications.

first: M

first: K

last: Wiegand

first: N

last: Melnyk

first: C

last: Chow

last: Salamanca

first: L

last: Prentice

first: J

last: Senz

first: W

last: Yang

last: Shumansky

first: D

last: Cochrane

last: Spillman

first: S

last: Shah

middle: E

last: Kalloger

middle: G

last: Huntsman


title: Next-generation sequencing of cancers of unknown primary (Affymetrix GenomeWideSNP data)

status: Public on Aug 07 2013

city: Melbourne

first: Richard

middle: William

last: Tothill

state: Victoria

address: St Andrews Place

department: Research

country: Australia

institute: Peter MacCallum Cancer Centre

summary: SNP 6.0 copy number analysis was done to validate results from next-generation sequencing read-depth CNV analysis in a cohort of cancers of unknown primary

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved tissue samples
7 samples

first: Prue

last: Cowin

first: David

last: Bowtell


title: Human epidermal stem cell function is regulated by circadian oscillations

status: Public on Sep 06 2013

city: Barcelona

first: Salvador

middle: Aznar

last: Benitah

address: Baldiri Reixac 10

department: Oncology

country: Spain

institute: Institute for Research in Biomedicine (IRB, Barcelona)

summary: Surveying epidermal stem cell homeostais over a 45-hour time course

overall_design: 45h time course with 10 samples over triplicates (x2 Agilent arrays)

last: Aznar-Benitah


title: Genome-wide methylation analysis of prostate tissues reveals global methylation patterns of prostate cancer

first: Yan P.

last: Yu

address: 3550 Terrace st.

department: Pathology

summary:
High-throughput analyses of concordant gene methylation and expression events were carried out for 91 human prostate specimens, including prostate cancer (T), matched normal adjacent to tumor (AT), and organ donor (OD).  Methylated DNA in genomic DNA was immunoprecipitated with anti-methylcytidine antibodies and detected by Affymetrix human whole genome SNP 6.0 chips.
Methylated genomic DNA was purified by 5-hmc antibodies and Affymetrix SNP arrays were performed according to the manufacturer's manual.

overall_design:
Copy number analysis of Affymetrix human SNP arrays was performed for both 5mc- and genomic DNA of prostate cancer samples. Methylations of genes were called when the allel amplification was reported in 5_mc DNA, and the background of the detection was suppressed by matched DNA sample.
we used copy number of each probe set as baseline to detect the enrichment of methylated DNA from the same sample.  Therefore, each specimen has two arrays; one is straight copy number (*SNP.CEL), another methylation enriched DNA (*5MC_SNP.CEL). Each CNV probe is based on the design from Affymetrix but no SNP ID was assigned.

first: Yan

middle: P

first: Jian-hua

last: Luo


title: Genomic profiling of Richter-syndrome Chronic Lymphocytic Leukemia

status: Public on Sep 20 2013

city: Bellinzona

first: Francesco

last: Bertoni

state: Ticino

address: Via V. Vela 6

department: Lymphoma & Genomics Research Program

country: Switzerland

institute: IOR

summary: Richter syndrome (RS) occurs in up to 15% of patients with chronic lymphocytic leukemia (CLL). While RS, usually represented by the histologic transformation to a diffuse large B-cell lymphoma (DLBCL), is associated with a very poor outcome, especially when clonally related to the pre-existing CLL, mechanisms leading to RS have not been clarified yet. To better understand the pathogenesis of RS, we analyzed a series of cases including: 59 RS, 28 CLL-phase of RS, 315 CLL and 127 de novo DLBCL. RS demonstrated a genomic complexity intermediate between CLL and DLBCL. Cell cycle deregulation via inactivation of TP53 and of CDKN2A was a main mechanism in the histologic transformation from CLL-phase, being present in approximately half of the cases, and affected the outcome of the RS patients. A second major subgroup was characterized by the presence of trisomy 12 and comprised one third of the cases. While RS shared some of the lesions seen in de novo DLBCL, its genomic profile was clearly separate. The CLL-phase preceding RS had not a generalized increase in genomic complexity when compared with untransformed CLL, but it presented clear differences in the frequency of specific genetic lesions.

first: Andrea

last: Rinaldi

first: Ivo

last: Kwee


title: Genome-wide SNP analysis of the Systemic Capillary Leak Syndrome (Clarkson disease)

status: Public on Jul 19 2013

city: Bethesda

first: Vijay

last: Nagarajan

state: Maryland

address: 10 Center Drive, 10/10N248

department: National Eye Institute

institute: National Institutes Of Health

summary: The Systemic Capillary Leak Syndrome (SCLS) is an extremely rare, orphan disease that resembles systemic anaphylaxis. The disorder is characterized by repeated, transient, and seemingly unprovoked episodes of hypotensive shock and peripheral edema due to transient endothelial hyperpermeability. SCLS is often accompanied by a monoclonal gammopathy of unknown significance (MGUS). Using Affymetrix Single Nucleotide Polymorphism (SNP) microarrays, we performed the first genome-wide SNP analysis of SCLS in a cohort of 12 disease subjects and 18 controls. Exome capture sequencing was performed on genomic DNA from nine of these patients as validation for the SNP-chip discoveries and de novo data generation. We identified candidate susceptibility loci for SCLS, which included a region flanking CAV3 (3p25.3) as well as SNP clusters in PON1 (7q21.3), PSORS1C1 (6p21.3), and CHCHD3 (7q33). Among the most highly ranked discoveries were gene-associated SNPs in the uncharacterized LOC100130480 gene (rs6417039, rs2004296). Top case-associated SNPs were observed in BTRC (rs1235580, 3rs4436485), ARHGEF18 (rs11668246), CDH13 (rs4782779), and EDG2 (rs12552348), which encode proteins with known or suspected roles in B cell function and/or vascular integrity. SNPs that were significantly associated with SCLS by microarray analysis were also detected and validated by exome deep sequencing. Functional annotation of highly ranked SNPs revealed enrichment of cell projections, cell junctions and adhesion, and molecules containing pleckstrin homology, Ras/Rho regulatory, and immunoglobulin Ig-like C2/fibronectin type III domains, all of which involve mechanistic functions that correlate with the SCLS phenotype. These results highlight SNPs with potential relevance to SCLS.

overall_design: Our study cohort included 12 patients with SCLS. The control group included 17 age, sex and ethnicity-matched healthy donors (including two relatives of SCLS patients), and a reference sample  supplied by the SNP-chip manufacturer (Affymetrix), for which age information was not available. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from purified B lymphocytes.

first: Zhihui

last: Xie

first: Vijayaraj

first: Daniel

last: Sturdevant

first: Shoko

last: Iwaki

first: Eunice

last: Chan

first: Laura

last: Wisch

first: Michael

last: Young

first: Celeste

last: Nelson

first: Stephen

middle: F

last: Porcella

first: Kirk

middle: M

last: Druey


title: Affymetrix SNP array data for myelodysplastic syndrome with 5q deletion treated with lenalidomide

status: Public on Jul 01 2013

city: Badalona

first: Mar

last: Mallo

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

institute: Josep Carreras Leukaemia Research Institute

summary: Lenalidome is a drug especially effective in low risk myelodysplastic syndromes (MDS) with isolated 5q deletion. However, 25% of the patients did not respond. TP53 mutations have been described to play a role in the disease progression, and karyotypic complexity also has an important impact in the outcome. We selected 53 MDS patients with 5q deletion and treated with lenalidomide and we studied by the following techniques: conventional G-banding cytogenetics (CC), single nucleotide polymorphism arrays (SNP-A) and sequencing, in order to assess their impact on treatment response and disease progression.   Low karyotypic complexity (by CC), a high baseline platelet count (>280x103/L) and TP53 unmutated gene status are associated with the achievement of hematological response (P=0.005, P=0.008 and P=0.057, respectively). In a multivariate model, the most important predictors for lenalidomide failure are karyotypic complexity (P=0.014) and a platelet count below 280x103/L (P=0.042). Additionally, none of the TP53 mutated cases achieved complete cytogenetics response. Nevertheless, inclusion of defects by SNP-A did not allow for a better separation of responders and non responders. These findings constitute a useful reference data to be considered before lenalidomide treatment enrollment.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from bone marrow or peripheral blood and, in some cases, also lymphocytes CD3 isolated from peripheral blood samples.
Copy number analyses of Affymetrix 250K and 6.0 SNP arrays were performed for 53 MDS with 5q deletion samples. There are also 30 samples from lymphocytes CD3 isolated from peripheral blood, which were used as germ-line DNA (control).

first: Monica

last: del Rey

first: Jesús

last: Hernández

first: Francesc

last: Solé

first: Jaroslaw

last: Maciejewski


title: Murine HCC development: comparison of wt, krt18+/- and krt18-/- liver tumors hybridized against non-affected wt liver tissue

status: Public on Jul 02 2013

city: Graz

first: Vendula

last: Svendova

address: Auenbruggerplatz 2

institute: Medical University Graz

summary: Analysis of the different genotype tumors revealed enhanced chromosomal aberrations in all tumors. The most chromosomal aberrations were found in the krt18-/- tumors.

overall_design: Two-condition experiment: wt (non-affected) liver tissue vs. wt tumor / krt18+/-tumor / krt18-/- tumor

first: Eva

last: Lederer

first: Monika

last: Mach


title: Affymetrix SNP array data for breast cancer samples

status: Public on Jun 29 2013

city: Bar Harbor

first: Edison

last: Liu

state: ME

address: 600 Main Street

institute: The Jackson Laboratory

summary: Chromosomal structural mutations play an important role in determining the transcriptional landscape of human breast cancers.  We determined that pro-oncogenic and anti-oncogenic genes are clustered throughout the genome and that these clusters coincide with regions of segmental amplification and deletion.  We constructed detailed structural mutation maps of representative breast cancers and found that tandem duplications appear to nucleate regions for amplification.  Subsequent rearrangements link distant pro-oncogenic elements for co-amplification, and are associated with loss of tumor suppressors.  We show that genes engaged in co-amplifications or conjoint deletions on 17q and 8q have pro-growth effects that are additive in nature.  Our results suggest structural mutations efficiently orchestrate the gain and loss of cancer gene cassettes that engage many oncogenic pathways simultaneously.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from fresh-frozen breast tumors with >80% tumor cell content and their paired peripheral blood samples.
Copy number analysis of the SNP arrays was done using the copy number pipeline implemented into Partek software version 6.5

first: Koichiro

last: Inaki

first: Alfredo

last: Hidalgo-Miranda