title: Microarray gene expression profiling of isolated class I and class IV Drosophila dendritic arborization sensory neurons

status: Public on Jul 21 2013

city: Fairfax

first: Daniel

middle: N

last: Cox

state: VA

address: 4400 University Drive, MSN 2A1

department: School of Systems Biology, Krasnow Institute

institute: George Mason University

summary:
Class I and IV Drosophila dendritic arborization sensory neurons were isolated via magnetic bead sorting and total RNA isolated from the samples was used for gene expression profiling.
Elucidating the molecular mechanisms controlling dendrite development is key to understanding the pivotal role these structures play in influencing synaptic integration and neural function.  Despite significant advances in this field, genetic pleiotropy remains a significant impediment to investigating such complex developmental processes.  To circumvent this problem, we have applied class specific neuron transcriptional expression profiling coupled to an in vivo RNAi functional validation screen in order to dissect the molecular bases of Drosophila class I and class IV dendritic arborization (da) neuron dendritogenesis.

overall_design: Gene expression profiling of class I and IV da neurons, isolated via magnetic bead sorting (using protocols as described in Iyer et al., 2009), was performed at the third instar larval stage of development from independent cell isolations from 40-50 age-matched third instar larvae expressing mCD8::GFP under the control of either  GAL4ppk.1.9 driver or Gal80ppk; GAL4221. For controls, age matched whole larval homogenate RNA was used.

first: Eswar

last: Iyer

first: Srividya


title: Genomic characterization of three acute lymphoblastic leukemia cases and one established cell line REH at the single cell level

status: Public on Jul 26 2013

city: London

first: Nicola

middle: Emma

last: Potter

state: Sutton, Surrey

address: 15 Cotswold Rd

department: Molecular Pathology

country: United Kingdom

institute: Institute of Cancer Research

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

summary:
DNA copy number alterations and mutations were characterised by bulk SNP anlaysis and exome sequencing (not sown here) in three acute lymphoblastic leukaemia samples and one establish cell line REH. Further single cell experiments of these cases investigated the mutation and copy number targets previously defined exploring the sub-clonal populations and phylogenic trees within each leukaemia.
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples.

overall_design: Copy number analysis of Affymetrix SNP6 arrays or Cytogenetics whole genome 2.7M arrays was performed for three leukaemic samples and one established cell line REH. Remission samples were only available for two of the leukaemia samples (Case A and Case B) and therefore 20 HapMap Caucasien samples were used as controls for the SNP6 array expeeriments.

first: M

last: Greaves

first: N

middle: E


title: Alteration of gene expression in human T cells treated with JPH203

status: Public on Jul 09 2013

city: Tochigi

first: Keitaro

last: Hayashi

address: 880 Kitakobayashi, Mibu, Shimotsuga

country: Japan

institute: Dokkyo Medical University

summary: To indentify the effect of JPH203 on the gene expression in activated T cells, microarray analysis was performed using activated human T cells derived from peripheral blood.  Human CD4+ T cells from peripheral blood in healthy volunteer  were activated with anti-CD3 and anti-CD28 in the presence of 1uM JPH203 for 3days. RNA was extracted and gene expression was compared between JPH203-treated cells and control cells.

overall_design: Gene epression of human peripheral blood CD4+ T cells  activated with anti-CD3 and anti-CD28 in the presence of 1uM JPH203 for 3days was measured.


title: Wild-Type Nras Lacks Tumor Suppressor Activity and Nras Oncogene Dosage Strongly Modulates Hematopoietic Transformation

status: Public on Jul 02 2013

city: Memphis

first: Shann-Ching

last: Chen

state: TN

address: 262 Danny Thomas Place

department: Pathology

country: USA

institute: St. Jude Children's Research Hospital

summary: Contemporary treatment of pediatric acute myeloid leukemia (AML) requires the assignment of patients to specific risk groups. To explore whether expression profiling of leukemic blasts could accurately distinguish between the known risk groups of AML, we analyzed 130 pediatric and 20 adult AML diagnostic bone marrow or peripheral blood samples using the Affymetrix U133A microarray.  Class discriminating genes were identified for each of the major prognostic subtypes of pediatric AML, including t(15;17)[PML-RARalpha], t(8;21)[AML1-ETO], inv(16) [CBFbeta-MYH11], MLL chimeric fusion genes, and cases classified as FAB-M7. When subsets of these genes were used in supervised learning algorithms, an overall classification accuracy of more than 93% was achieved.  Moreover, we were able to use the expression signatures generated from the pediatric samples to accurately classify adult de novo AMLs with the same genetic lesions. The class discriminating genes also provided novel insights into the molecular pathobiology of these leukemias.  Finally, using a combined pediatric data set of 130 AMLs and 137 acute lymphoblastic leukemias, we identified an expression signature for cases with MLL chimeric fusion genes irrespective of lineage. Surprisingly, AMLs containing partial tandem duplications of MLL failed to cluster with MLL chimeric fusion gene cases, suggesting a significant difference in their underlying mechanism of transformation.  All the gene expression arrays are available through http://www.stjuderesearch.org/site/data/AML1/ in the original study (PMID:15226186).  To study the RAS gene expression in the human AML patients, a total of 104 AML cases with known KRAS and NRAS status (including 72 gene expression arrays in the original study and 32 additional arrays acquired later on), as well as 4 CD34+ normal bone marrow cases deposited in GEO GSE33315, were including in this depository.

overall_design: Gene expression profiling was performed on 104 single diagnosis tumor samples and 4 CD34+ normal bone marrow samples

first: Mary

last: Ross

first: James

middle: R

last: Downing


title: Affymetrix_SNP6_Allelotyping

status: Public on Jun 22 2013

city: Greifswald

first: Georg

last: Homuth

address: F.-L.-Jahn-Str. 15a

department: Interfaculty Institute for Genetics and Functional Genomics

country: Germany

institute: University Medicine Greifswald

summary:
Comparison of Genotyping using pooled DNA samples (Allelotyping) and Individual Genotyping using the Affymetrix Genome-Wide Human SNP Array 6.0
In this study, data from 100 DNA samples individually genotyped with the Affymetrix Genome-Wide Human SNP Array 6.0 were used to estimate the error of the pooling approach by comparing the results with those obtained using the same array type but DNA pools each composed of 50 of the same samples. Newly developed and established methods for signal intensity correction were applied. Furthermore, the relative allele intensity signals (RAS) obtained by allelotyping were compared to the corresponding values derived from individual genotyping. Similarly, differences in RAS values between pools were determined and compared.

overall_design: 2 disjunct DNA pools each composed of 50 samples, incl. one technical replicate each.

first: Alexander

last: Teumer

first: Florian

middle: D

last: Ernst

first: Anja

last: Wiechert

first: Katharina

last: Uhr

first: Matthias

last: Nauck

first: Astrid

last: Petersmann

first: Henry

last: Völzke

first: Uwe

last: Völker


title: Multi-region copy-number analysis

status: Public on Jun 04 2013

city: Lyon cedex 08

first: Pierre

last: Martinez

address: 28 rue Laennec

country: France

institute: Cancer Research Centre of Lyon

summary:
Intra-tumour heterogeneity (ITH) foster tumour adaptation and hamper the efficiency of personalised medicine approaches. We investigated the extent of ITH within individual clear cell renal cell carcinomas (ccRCC) by multi-region sampling and copy number analysis.
We analyzed 63 tumour regions and 8 normal samples from eight clear cell renal cell carcinomas using Affymetrix SNP6 arrays.

overall_design: All individual tumours were subjected to multi-region sampling and copy-number analysis using Affymetrix SNP6 arrays.

first: Andrew

last: Rowan

first: Charles

last: Swanton


title: Gene expression signatures in HuH7 cells transfected with super hybrid p53 version 2.

status: Public on May 23 2013

city: Sapporo

first: Yasushi

last: Sasaki

address: S-1, W-17, Chuo-ku

department: Cancer Research Institute

institute: Sapporo Medical University

summary: The p53 tumor suppressor belongs to a gene family that includes two other structurally and functionally related members: p63 and p73. However, the regulation of p53 activity differs significantly from that of p73 and p63. To enhance the tumor suppressive activity of p53, we created a p63/p53 hybrid molecule, named p63-53O, which comprises the transcriptional activation and DNA-binding domains of TAp63γ and the oligomerization domain of p53. In this study, we generated a series of p63-53O derivatives and developed an advanced hybrid molecule named “Super Hybrid p53 (SHp53).” SHp53 efficiently transactivated several proapoptotic genes, including CASP10, KCNK3, and PYCARD, compared with p53. Moreover, the silencing of these proapoptotic genes partially abolished the apoptotic response to SHp53 in human cancer cells. The potency of SHp53 for suppressing tumorigenesis was also evaluated using in vivo models. Thus, our results identify a better p63/p53 hybrid molecule for the development of anti-cancer therapies.

overall_design: HuH-7 human hepatocellular carcinoma cells were either transduced with adenoviral vectors expressing p53, TAp63gamma, p53-p63 hybrid (super hybrid p53 version 2, p63-53O-FL), or lacZ. After 24 hours, total RNA was isolated and analyzed by hybridization to Agilent-028004 SurePrint G3 Human GE 8x60K Microarray.

first: Lisa

last: Kashima

first: Takashi

last: Tokino


title: C/EBPα induces highly efficient macrophage transdifferentiation of selected B-lymphoma /leukemia cell lines and impairs their tumorigenicity

status: Public on Mar 14 2013

city: Barcelona

first: Francesca

last: Rapino

address: dr.aiguader 88

country: Spain

institute: center for genomic regulation

summary: Earlier work demonstrated that the transcription factor C/EBPα can convert immature and mature murine B lineage cells into functional macrophages. Testing >20 human lymphoma and leukemia B-cell lines, we found that most can be transdifferentiated at least partially into macrophage-like cells, provided that C/EBPα is expressed at sufficiently high levels. A tamoxifen-inducible subclone of the Seraphina Burkitt lymphoma line, expressing C/EBPαER, could be efficiently converted into phagocytic and quiescent cells with a transcriptome resembling normal macrophages. The converted cells retained their phenotype even when C/EBPα was inactivated, a hallmark of cell reprogramming. Interestingly, C/EBPα induction also impaired the cells' tumorigenicity. Likewise, C/EBPα efficiently converted a B- lymphoblastic leukemia cell line into macrophage-like cells, again dramatically impairing their tumorigenicity. Our experiments show that human cancer cells can be induced to transdifferentiate by C/EBPα into seemingly normal cells at high frequencies and provide a proof of principle for a potential new therapeutic strategy to treat B-cell malignancies.

overall_design: Changes in gene expression during transdifferentiation of BLaER1 cells, comparing uninduced (0h) cells with cells treated with E2 for 3h, 6h, 9h, 12h, 18h, 24h, 36h, 48h, 72h, 120h or 168h. Primary human B-cells and macrophages were used as controls. 2 replicates each.

first: Eloy

middle: F

last: Robles

first: Jose

middle: A

last: Richter-Larrea

first: Eric

middle: M

last: Kallin

last: Martinez-Climent

first: Thomas

last: Graf


title: Genome-wide screening of the expression of long noncoding RNA and coding RNA expression in esophageal sqaumous cell cancer

status: Public on Mar 21 2013

city: Calgary

first: Wei

last: Wu

address: 3330 Hospital Dr. NW

country: Canada

institute: 1.Zhengzhou Central Hospital, Affiliated to Zhengzhou University, China; 2. University of Calgary

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

summary: In order to understand the role of long noncoding RNAs (lncRNAs) and their interaction with coding RNAs in esophageal sqaumous cell cancer (ESCC), we performed genome-wide screening of the expression of lncRNAs and coding RNAs from primary ESCC tissue and adjacent normal tissue using Agilent SurePrint G3 Human GE 8x60K Microarray. By comparing ESCC tissues and matched normal tissues, differentially expressed lncRNAs and coding RNAs were identified and confirmed with PCR and other independent studies. We further identified a subset of co-located and co-expressed lncRNAs and coding RNAs using bioinformatic tools and the analysis suggested that a subset of lncRNAs may influence nearby genes involved in the genesis of ESCC.

overall_design: Four pairs of ESCC primary tumors and adjacent normal tissues were used for genome-scale microarray experiments, which included long noncoding RNAs and coding RNAs. Selected lncRNAs expressed in the experiment were validated on independent matched-pair samples with PCR method.

last: Cao

first: Fachun

last: Shi


title: miR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines.

status: Public on Apr 01 2013

city: Valbonne - Sophia-Antipolis

first: Kevin

last: Lebrigand

address: 660 route des lucioles

institute: IPMC/CNRS

summary: The resistance of hypoxic cells to radiotherapy and chemotherapy is a major problem in the treatment of cancer. Recently, an additional level of Hypoxia Inducible Factor (HIF) dependent transcriptional regulation has emerged involving modulation of a specific set of miRNAs including miR-210. We have recently shown that HIF-1 induction of miR-210 also stabilizes HIF-1 through a positive regulatory loop. We therefore hypothesized that by stabilizing HIF-1 in normoxia, miR-210 may protect cancer cells from radiation. We developed Non-Small Cell Lung Cancer (NSCLC)-derived cell lines (A549 and H1975) stably expressing miR-210 (pmiR-210) or a control miRNA (pmiR-Ctl). MiR-210 expressing cells showed a significant stabilization of HIF-1 associated with mitochondrial defects and a glycolytic phenotype. The cells were subjected to radiation levels ranging from 0 to 10Gy in normoxia and hypoxia. Cells expressing miR-210 in normoxia had the same level of resistance than control cells in hypoxia. pmiR-210 cells under hypoxia showed a low mortality rate due to a decrease in apoptosis and an ability to grow even at 10Gy. We have established that radioresistance was independent of p53 and cell cycle status. In addition, we show here that genomic double strand breaks (DSB) foci disappeared faster in pmiR-210 than in pmiR-Ctl cells, suggesting that miR-210 expression promotes a more efficient DSB repair. Finally, HIF-1 invalidation in pmiR-210 cells (pmiR-210/HIF-1-) abolished radioresistance of cells showing that this mechanism was dependent upon HIF-1. In conclusion, miR-210 appears to be a major component in the radioresistance of hypoxic cancer cells. Given the high stability of most miRNAs, this advantage could even be used by tumor cells in conditions where hypoxia may not be present anymore and strongly suggests that strategies targeting miR-210 would enhance tumor radiosensitization.

overall_design: To identify the set of transcripts targeted by miR-210, we overexpressed has-miR-210 or a control miRNA (ce-miR-67) in human lung adenocarcinoma A549 cells by transduction using lentivirus. The resulting pmiR-67 and pmiR-210 that stably overexpress miR-210 were selected by puromycin. RNA samples were harvested at 2 different times following cell plating (24 hours or 48 hours). Experiments were performed in dye-swap.

first: S

last: Grosso

first: P

last: Barbry

first: B

last: Mari

first: K


title: Clonal evolution, genomic drivers, and effects of therapy in chronic lymphocytic leukemia

status: Public on Apr 19 2013

city: Ann Arbor

first: Sami

last: Malek

state: MI

address: 4410 Cancer Center; 1500 E Medical Center Dr

department: Internal Medicine, Hematology-Oncology

institute: University of Michigan

summary:
The identification of gene mutation and structural genomic aberrations that are critically involved in CLL pathogenesis is still evolving.  One may postulate that genomic driver lesions with effects on CLL proliferation, apoptosis thresholds, or chemotherapy resistance should increase in frequency over time when measured sequentially in a large CLL cohort.  We sequentially sampled a large, well-characterized CLL cohort at a mean of 4 years between samplings.  The paired analysis included 156 patients, of whom 114 remained untreated and 42 received intercurrent therapies.  Results:  we identify a strong effect of intercurrent therapies on the frequency of acquisition of aCNAs in CLL.  Importantly, the spectrum of acquired genomic changes was largely similar in patients that did or did not receive intercurrent therapies; therefore, various genomic changes that become part of the dominant clones are often already present in CLL cell populations prior to therapy.  Further, we provide evidence that therapy of CLL with preexisting TP53 mutations results in the outgrowth of genomically very complex clones which dominate at relapse.
Using complementary technologies directed at the detection of genomic events that are present in substantial proportions of of the clinically relevant CLL disease bulk, we capture aspects of genomic evolution in CLL over time, including increases in the frequency of genomic complexity, specific recurrent aCNAs, and TP53 mutations.

overall_design: Data from 156 paired samples (enrollment and one longitudinal sample) are included in this data set.  Of these, 27 patients were assayed at two (or, rarely, more than two) time points.  Please note: normal DNA and enrollment date tumor DNA CEL files and SNP call files  will be found in a separate GEO data submission:  GSE30777

first: Peter

last: Ouillette

first: Kamlai

last: Saiya-Cork

first: Erlene

last: Seymour

first: Cheng

last: Li

first: Kerby

last: Shedden


title: Genomic changes in low vs high metastatic A549 NSCLC cell line

status: Public on Feb 21 2013

city: Münster

first: Nils

middle: H

last: Thoennissen

address: Albert-Schweitzer-Str. 33

department: Hematology Oncology

institute: University Hospital of Münster

summary: Genomic changes in low and highly metastatic A549 cells were analyzed by 500K SNP arrays. A large number of genomic alterations were present in A549 cells but no significant differences were observed between the low or highly metastatic A549 cell lines.

overall_design: We generated a NSCLC line with highly increased propensity to form tumor nodules in murine lungs after intravenous injections. Extravasation and growth at a distant site are important parts of the metastatic process and we regarded these as a surrogate marker for in vivo aggressiveness and potential metastatic capability. A549 lung asdenocarcimona cell line with initially low metastatic potential was used for this purpose; these cells formed multiple small nodules in NOD/SCID mice after first i.v.-injection, round 1 (R1). Removal of tumor nodules from the lungs and subsequent re-injection led to a rapid increase in metastatic capacity. A highly aggressive phenotype which was stable over time was evident after three rounds (R3) of in vivo selection for the A549 cell line.


title: Affymetrix SNP array data for different passages of mesenchymal stem cells.

status: Public on Feb 15 2013

city: Aachen

first: Lin

last: Gan

address: Pauwelsstr. 30

department: IZKF

institute: University Hospital Aachen

summary: Cells in culture undergo replicative senescence and unequivocally stop proliferation after a limited number of cell divisions. In this study, we have expanded mesenchymal stem cells (MSC) from human adipose tissue and analyzed genetic and epigenetic sequels. The subpopulation of highly proliferative cells and the in vitro differentiation potential decayed already within early passages. Relevant chromosomal aberrations were not detected by karyotyping and SNP-microarrays.

overall_design: Comparison of early and late passage of five samples of mesenchymal stem cells from human adipose tissue.

first: Anne

last: Schellenberg

first: Qiong

last: Lin

first: Herdit

last: Schüler

first: Carmen

last: Koch

first: Silvia

last: Joussen

first: Bernd

last: Denecke

first: Gudrun

last: Bokermann

first: Norbert

last: Pallua

first: Christoph

middle: V

last: Suschek

first: Martin

last: Zenke

first: Wolfgang

last: Wagner


title: Gene copy number variations associated with patient survival in uveal melanoma

status: Public on Feb 01 2013

city: Liverpool

first: Sarah

last: Lake

address: 6th Floor, Duncan Building, Daulby Street

department: Molecular and Clinical Cancer Medicine

institute: University of Liverpool

summary:
Analysis of DNA from fixed tissues specimens of 58 primary uveal melanomas, with known clinical outcome, to determine gene copy number variations that were associated with survival.
Abstract: Uveal melanomas can be stratified into subgroups with high or low risk of metastatic death, according to the presence of gross chromosomal abnormalities. Where a monosomy 3 uveal melanoma is detected, patient survival at three years is reduced to 50%. However, approximately 5% of patients with a disomy 3 tumour ultimately develop metastasis, and a further 5% of monosomy 3 uveal melanoma patients’ exhibit disease-free survival for more than five years. Despite extensive knowledge of the chromosomal abnormalities occurring in uveal melanoma, the genes driving metastasis are not well defined. Gene copy number variations occurring in a well-characterised cohort of 58 formalin-fixed, paraffin-embedded uveal melanoma samples were identified using the Affymetrix SNP 6.0 whole genome microarray.  Four genetic sub-groups of primary uveal melanoma were represented in the patient cohort: 1) disomy 3 with long-term survival; 2) metastasizing disomy 3; 3) metastasizing monosomy 3; and 4) monosomy 3 with long-term survival. Cox regression and Kaplan-Meier survival analysis identified three genes that were associated with differences in patient survival. Patients with an amplification of CNKSR3 (6q) or RIPK1 (6p) demonstrated longer survival than those with gene deletions or no copy number change (log rank, p=0.022 and p<0.001, respectively). Conversely, those patients with an amplification of PENK (8q) showed reduced survival (log rank p<0.001). CNKSR3, RIPK1 and PENK are novel candidate metastasis regulatory genes in uveal melanoma. This is the first report of amplification of a specific gene on 6p that is associated with improved uveal melanoma patient survival and suggests that the development of uveal melanomas with a propensity to metastasise may be limited by genes on 6p.

overall_design: 58 samples in total.  Ten disomy 3 with long-term survival. Fifteen disomy 3 with metastasising. Seventeen monosomy 3 with long-term survival. Sixteen monosomy 3 metastasising.

middle: L

first: Bertil

last: Damato

first: Azzam

last: Taktak

first: Bryony

last: Lloyd

last: Coupland


title: Genetic adaptability of cancer cells under treatment selection pressure in multiple myeloma patients.

status: Public on Feb 13 2013

city: Saint Herblain

first: Wilfried

last: Gouraud

address: bd Jacques Monod

department: Integrated Center of Oncology René Gauducheau

institute: ICO (Integrated Center of Oncology Nantes)

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

summary:
Purpose

Despite advances and significant improvement in survival, multiple myeloma (MM) remains incurable and nearly all patients relapse after treatment. Previous studies have shown a complex spectrum of diverse genetic alterations in almost all patients, but evolution of genomic rearrangements throughout myeloma life cycle has not been investigated.

Patients and Methods

We performed genomic analysis integrating copy number, allele specific copy number, allele ratio calculations, breakpoint sequencing and rearrangement PCR genotyping on matched diagnosis and relapse samples from 24 MM patients either treated with proteasome inhibitor (bortezomib)-based induction regimen or conventional chemotherapeutic agents.

Results

All relapse samples have a clear relationship to the diagnosis clone with  significant increase of copy number abnormalities (CNAs). Despite a wide diversity of CNAs acquired at relapse, regulators of NF-kB activity were targeted in 25% of the patients. Relapse-associated lesions either appeared as new acquisition or were selected from minor subpopulations at diagnosis. In one third of the patients, we found loss of abnormities containing loss of heterozygosity (LOH) providing evidence that the relapse clone derived from an ancestral clone shared with the dominant diagnosis clone. Remarkably, re-emergence of ancestral clones was almost exclusively found in patients treated with bortezomib, attested to a remarkable adaptability of myeloma cells under targeted drug selection pressure.

Conclusion

These data suggest that genomic instability and clonal selection are the main forces that drive adaptive changes in MM under drug selection pressure, and they support the proposal to combine several anti-myeloma drugs upfront in order to obtain long-term remissions.

overall_design: [SNP genotyping] 24 myeloma patients at diagnosis and relapse examined with high resolution genome-wide chip

first: Florence

last: Magrangeas

first: Hervé

last: Avet-Loiseau

first: Olivier

last: Decaux

first: Kenneth

middle: C

last: Anderson

first: Philippe

last: Moreau

first: Nikhil

last: Munshi

first: Stéphane

last: Minvielle


title: Clonal evolution and devolution following chemotherapy in adult acute myelogenous leukemia

status: Public on Feb 12 2013

first: Sami

last: Malek

summary: The frequent occurrence of persistent or relapsed disease following induction chemotherapy in AML necessitates a better understanding of the clonal relationship of AML in various disease phases. In this study, we employed SNP 6.0 array-based genomic profiling of acquired copy number aberrations (aCNA) and copy neutral LOH (cnLOH) together with sequence analysis of recurrently mutated genes to characterize paired AML genomes. We analyzed 28 AML sample pairs from patients that achieved complete remission with chemotherapy and subsequently relapsed and 11 sample pairs from patients with persistent disease following induction chemotherapy. Through review of aCNA/cnLOH and gene mutation profiles in informative cases we demonstrate that relapsed AML invariably represents reemergence or evolution of a founder clone. Furthermore, all individual aCNA or cnLOH detected at presentation persisted at relapse indicating that this lesion type is proximally involved in AML evolution. Analysis of informative paired persistent AML disease samples uncovered cases with two coexisting dominant clones of which at least one was chemotherapy sensitive and one resistant, respectively. These data support the conclusion that incomplete eradication of AML founder clones rather than stochastic emergence of fully unrelated novel clones underlies AML relapse and persistence with direct implications for clinical AML research

overall_design: This study is based on 39 patients with AML for which either paired enrollment or relapse samples or persistent disease samples were available. The patients were enrolled into this study at the University of Michigan Comprehensive Cancer Center. The study was approved by the University of Michigan Institutional Review Board (IRBMED #2004-1022) and written informed consent was obtained from all patients prior to enrollment.   Genomic DNA was extracted from purified AML blasts and paired buccal cells.  DNA thus obtained was hybridized to Affymetrix SNP 6.0 arrays. Note: There is no normal sample available for MIAML015.

first: Brian

last: Parkin

first: Peter

last: Ouillette

first: Yifeng

last: Li

first: Jennifer

last: Keller

first: Cindy

last: Lam

first: Diane

last: Roulston

first: Cheng

first: Kerby

last: Shedden


title: Affymetrix SNP and CNV data for the HuRef individual

city: Toronto

first: Andy

last: Pang

state: ON

address: MaRS Centre - East Tower, 101 College Street, Room 14-701

institute: The Centre for Applied Genomics

summary: The ideal genome sequence for medical interpretation is complete and diploid, capturing the full spectrum of genetic variation.  Toward this end, there has been progress in discovery of single nucleotide polymorphism (SNP) and small (<10bp) insertion/deletions (indels), but annotation of larger structural variation (SV) including copy number variation (CNV) has been less comprehensive, even with available diploid sequence assemblies. We applied a multi-step sequence and microarray-based analysis to identify numerous previously unknown SVs within the first genome sequence reported from an individual.

overall_design:
An Affymetrix SNP array experiment was performed according to the manufacturer's directions on DNA extracted from a lymphoblastoid cell line (HuRef).
Copy number analysis of Affymetrix 6.0 SNP arrays was performed for the HuRef sample. The HuRef sample was run in a batch of 50 control samples, which were used as baseline for calling CNVs.

middle: W


title: DNA methylation profiling of normal prostates and prostate cancer metastases [Affymetrix]

status: Public on Feb 04 2013

city: Charlestown

first: Martin

last: Aryee

state: MA

address: 149 13th Street

institute: Massachusetts General Hospital

summary: DNA methylation profiling of normal prostates from organ donors and prostate cancer metastases from a rapid autopsy cohort of lethal metastatic prostate cancer

overall_design: Multiple anatomically distinct metastases from each of five patients. Normal prostate samples from organ donors

middle: J

first: Srinivasan

last: Yegnasubramanian


title: Molecular Subtypes in Head and Neck Cancer

status: Public on Mar 01 2013

city: Chapel Hill

first: Vonn

last: Walter

state: NC

address: CB#7295, School of Medicine

institute: Lineberger Comprehensive Cancer Center

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

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

overall_design: Refer to individual Series


title: MiR-199a-5p determines fibroblast activation and pulmonary fibrogenesis

first: Kevin

last: Lebrigand

summary:
Idiopathic pulmonary fibrosis (IPF) is a chronic and often fatal pulmonary disorder characterized by fibroblast proliferation and the excess deposit of extracellular matrix proteins. The etiology of IPF is unknown, but a central role for microRNAs (miRNAs), a class of small non-coding regulatory RNAs, has been recently suggested. We report the upregulation of miR-199a-5p in mouse lungs undergoing bleomycin-induced fibrosis and also in human biopsies from IPF patients. Levels of miR-199a-5p were increased selectively in myofibroblasts and putative profibrotic effects of miR-199a-5p were further investigated in cultured lung fibroblasts. MiR-199a-5p expression was induced upon TGFβ exposure and ectopic expression of miR-199a-5p was sufficient to promote the pathogenic activation of pulmonary fibroblasts. CAV1, a critical mediator of pulmonary fibrosis, was established as a bona fide target of miR-199a-5p. Finally, we also found an aberrant expression of miR-199a-5p in mouse models of kidney and liver fibrosis, suggesting that dysregulation of miR-199a-5p represents a general mechanism contributing to the fibrotic process. We propose miR-199a-5p as a major regulator of fibrosis that represents a potential therapeutic target to treat fibroproliferative diseases.

This SuperSeries is composed of the SubSeries listed below.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

first: Bernard

last: Mari

first: Nicolas

last: Pottier

first: Pascal

last: Barbry

first: Imène

last: Hénaoui


title: Impact of miR-199-5p overexpression and CAV1 silencing on human lung fibroblasts

summary: To identify putative novel specific targets of mir-199-5p, we overexpressed miR-199a-5p as well as miR-21 and a siRNA targeted against CAV1 in  human HFL1 pulmonary fibroblasts (CCL-153)  by transfecting them with synthetic pre-miRNAs or a synthetic “negative” pre-miRNA as control (miR-Neg). RNA samples were harvested at 48 hours post-transfection and 2 independent experiments were carried out. Additional samples correspond to HFL1 cells  treated or not with 10ng/ml TGFbeta for 48 hours in the absence of serum (2 independent experiments).

overall_design: 2 independent experiments performed in a one color design, corresponding to 7 conditions (miR-Neg, miR-199-5p, miR-21, si-Neg, si-CAV1, control, TGFbeta) and a total of 14 samples.

first: B

first: P

first: K


title: Elimination of mitochondrial DNA variants by nuclear genome transfer in human oocytes.

status: Public on Jan 01 2013

city: New York

first: Daniel

last: Paull

address: 1995 Broadway

institute: The New York Stem Cell Foundation

summary:
Nuclear genome exchange between different oocytes results in efficient development and stem cell derivation.
No differences in homozgyous CNVs were found between swaPS and pES lines. No differences in total copy number variations were found between the swaPS and pES lines.

overall_design: DNA was isolated from cultured cells. Affymetrix SNP arrays were used in accordance with the manufacturer's instructions. Copy number analysis was performed using NEXUS 6.0.

first: Dieter

last: Egli


title: High-resolution genomic profiling of marginal zone B-cell lymphomas and variants

status: Public on Jan 11 2013

city: Ulm

first: Karlheinz

last: Holzmann

address: Helmholtzstreet 8/1

department: Medical Faculty

institute: Ulm University

summary: We studied marginal zone B-cell lymphomas of the gastrointestinal tract including seven small cell MALT lymphomas, eight composite lymphomas and thirteen large cell variants using SNP-array profiling. We found an increase of genomic complexity with lymphoma progression, and could identify gains of prominent (proto)oncogenes REL, ETS1, PTPN1, PTEN and KRAS that were associated exclusively with the large cell presentation of MALT lymphoma. Losses of ADAM3A and SCAPER, as well as gains of SIRPB1 occur during progression from small cell to large cell lymphoma. In two case studies, we examined lymphoma progression comparing two different regions of the same tumor and material acquired at two different time points from another lymphoma. Our analyses reveal genomic heterogeneity in both cases, supporting the theory of an oligoclonal tumor evolution model for MALT lymphomas and its variants.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved tumor samples.
Copy number and loss of heterozygosity analysis of Affymetrix GenomeWide SNP 6.0 arrays was performed for 7 small cell MALT lymphomas, 8 large cell areas of Composite lymphomas and 13 large cell variants. Two independant hybridizations of one of the small cell MALT lymphoma and one of the large cell areas of Composite lymphoma Samples were performed.

first: Lucia

last: Flossbach

first: Thomas

last: Barth


title: Molecular Subtypes in Head and Neck Cancer [copy number]

summary:
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease whose
underlying etiology has not been explained by traditional prognostic factors such as tumor site, stage, or histology. Although previous studies have shown that molecular subtypes of HNSCC exist, the benefit of such a classification scheme has not been fully realized. We show that molecular subtypes of HNSCC exist; that these subtypes have distinct patterns of chromosomal gain and loss, some of which affect canonical oncogenes and tumor suppressors; and that the subtypes are biologically and clinically relevant. These subtypes provide new insight into HNSCC etiology, as well as a valuable method for classifying HNSCC tumors.

overall_design: A total of 141 samples were considered. CEL files were subject to quality control (QC) procedures using the Affymetrix Genotyping Console, and arrays that produced contrast QC measurements above the default threshold of .4 were removed from subsequent analysis. The remaining 99 CEL files were processed with aroma, and log2 intensity ratios were produced using a pooled collection of normal samples as a reference. After segmenting the log2 ratios with DNAcopy, the resulting copy number profiles were subjected to manual review. Arrays that produced low quality copy number profiles were removed from subsequent analysis. Copy number values from chr1 - chr22 were considered.


title: Human bone marrow mesenchymal stem cells, young vs. old donors, early vs. late passages

status: Public on Apr 05 2013

city: Tampere

first: Dario

last: Greco

address: Arvo ylpön Katu 34

department: Faculty of Medicine and Health Technology

country: Finland

institute: Tampere University

summary: Mesenchymal stem/stromal cells (MSCs) with immunosuppressive properties are increasingly used in advanced cellular therapies. Since the clinical use of hMSCs demands sequential cell expansions, we studied the effect of cell doublings on the phospholipid profile as well as functionality of human bone marrow mesenchymal stem cells (hBMSCs). In addition to the structural role of phospholipids in cell membranes, they provide precursors for eicosanoids and other signalling lipids modulating cellular functions. The hBMSCs, harvested from young adult and old donors (n=5 for both), showed clear compositional changes during cultivation, seen at the level of lipid classes, lipid species and acyl chains. As the main finding at the lipid class level, the ratio of phosphatidylinositol to phosphatidylserine was increased towards the late passage samples. In the species profiles, arachidonic acid (AA) containing species of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) clearly accumulated, while the species containing monounsaturated fatty acids decreased. This was related with an increase of AA, a major n-6 polyunsaturated fatty acid (n-6PUFA), in the total fatty acid pool of the cells, which happened at the expense of n-3PUFAs, especially docosahexenoic acid (DHA). Using hBMSCs from four of the young adult donors and four of the old donors, we found that gene expression of several enzymes involved in fatty acid metabolism (such as FADS1, FADS2 and SCD) was altered. The expression of genes related to the regulation of cell cycle, senescence and immunomodulation were altered. Our findings suggest that multistep expansion of hBMSCs alters their fatty acid metabolism and membrane phospholipid composition, which affects lipid signalling and eventually the immune function of the cells.

overall_design: Cultured undifferentiated bone marrow-derived MSCs from old and young donors. Biological replicates: 4 old donors and 4 young donors, passages 4 and 8 from each.

first: Saara

last: Laitinen

first: Lotta

last: Kilpinen


title: SNP data from genomic DNA in patient with rectal cancer

status: Public on Dec 31 2012

city: daejeon

first: Tae-Wook

last: Kang

address: 111 Gwahangno, Yuseong-gu

country: South Korea

institute: KRIBB

summary: The identification of surrogate single nucleotide polymorphism (SNP) markers that can predict responses to preoperative chemoradiotherapy (CRT) in rectal cancer patients. Genome-wide association studies in clinical populations are theoretically capable of identifying markers that are capable of tumor regression after CRT. We used Affymetrix’s SNP Array 6.0 to detail genetic polymorphism of patient’s group showing differential responsiveness to preoperative CRT and profiled SNP biomarkers.

overall_design: The chemoradiosensitivity of tumor tissue from the initial cohort of 43 patients was assessed using clinical responses of tumor regression grade (TRG). TRG was clinically categorized as complete response (CR) as TRG 1, dominant response (ER or finally as DR) as TRG 1 and 2, and efficient response (RYN or finally as ER) as TRG 1, 2, and 3 (TRG grade from Mandard et al, 1994). Blood DNAs were prepared from each patients and hybridized to Affymetrix’s SNP Array 6.0. Genotypes were determined using the Affymetrix Genotyping Console software (version 2.1) based on the BRLMM-P algorithm. We used an ANOVA test to identify SNPs associated with quantitative TRG responses.

first: Jin

last: Kim

first: Seun-Young

first: Yong

middle: S


title: Genomic profiles vary with race and subtype in young African American and European American breast cancer (SNP)

status: Public on Jan 29 2013

city: Birmingham

first: Theresa

last: Strong

state: AL

address: 1530 3rd Avenue South

department: Medicine

institute: University of Alabama at Birmingham

summary: In the United States, African-American (AA) women are more likely to develop early-onset breast cancer and have historically poorer outcomes due to this disease compared to European-American (EA) women. Here, we analyzed genomic profiles of breast tumors from young women (<50 years old), matched by tumor subtype, histological grade, and ethnicity (African-American, AA, compared to European-American, EA). DNA copy number alterations (CNAs) were analyzed on the Affymetrix Human SNP Array v 6.0 platform. The study provides insight into the genetic component of ethnicity-related breast cancer health disparities.

overall_design:
DNA copy number alterations (CNAs) and genotypes were analyzed using the Affymetrix SNP 6.0 platform.
Breast tumor samples from young women (< 50 years old) were matched as follows: a matched pair consists of one AA and one EA sample, matched for tumor grade and tumor subtype (based on immunohistochemical analysis of ER, PR, and HER2 status). DNA from forty-four samples (22 AA, 22 EA) was analyzed on the Affymetrix SNP 6.0 array according to manufacturer’s directions.

first: Tyesha

last: Farmer


title: Identification of DNA palindromes in the MCF-7 breast cancer cell line

status: Public on Jan 25 2013

city: Frederick

first: Jack

last: Chen

state: MD

address: SAIC-Frederick Miller Dr

institute: NIH

summary: DNA palindromes are implicated as a causative agent in cancer formation due to their association with genomic instability and DNA amplification. However, the unique properties of palindromes render them refractory to current methods of analyses including PCR amplification and cloning into bacterial vectors.

overall_design: Genomic DNA was isolated from 3 million cells. One microgram of genomic DNA was labeled using SNP6 core reagent kit and hybridized onto Genome-wide human SNP Array 6.0.

first: Hui

last: Yang

first: Natalia

last: Volfovsky

first: Alison

last: Rattray

first: Xiongfong

first: Hisashi

last: Tanaka

first: Jeffrey

last: Strathern


title: Genomic profiles vary with race and subtype in young African American and European American breast cancer

type: Genome variation profiling by genome tiling array


title: Gene expression profile of the human leukemia cell line Reh after treatment with bortezomib, valproic acid or a combination of both.

city: Berlin

first: Shabnam

last: Shalapour

address: Augustenburger Platz 1

institute: Charité - Universitätsmedizin Berlin

summary: New therapy options are required for relapsed B-cell precursor ALL patients in order to improve survival and reduce adverse acute and late effects. We observed a synergistic anti-leukemic activity of concomitant treatment with bortezomib and valproic acid in BCP-ALL cells.  In this experiment we aimed to identify the pathways modulated after concomitant treatment with bortezomib and valproic acid.

overall_design: Reh cells treated with either bortezomib, valproic acid, or the combination of both normalized to a untreated control.


title: Human fetal chylothorax: pleural fluid vs. ascites fluid

city: Changhua

first: Gwo-Chin

last: Ma

address: 3F, 176, Zhanghua Rd.

department: Department of Genomic Medicine

country: Taiwan

institute: Changhua Christian Hospital

summary: Transcriptional profile comparison of the pleural and ascites fluids in hydropic fetuses affected with chylothorax.

overall_design: Two-condition experiment, pleural fluid vs. ascites fluid. Comparison of the transcriptional profile between sample collected before and after OK-432 treatment and between fetuses with and without a G404S mutation in the ITGA9 gene

first: Yi-Shing

last: Lin

first: Ming


title: Comparison of Cancer-Associated Genetic Abnormalities in Columnar-Lined Esophagus with and without Goblet Cells

status: Public on Dec 15 2012

city: Rochester

first: Santhoshi

last: Bandla

state: NY

address: 601 Elmwood Ave. Wilmot Cancer Center (3-0771)

department: Surgery

institute: University of Rochester Medical Center

summary: The requirement of goblet cells (intestinal metaplasia; IM) to define Barrett’s esophagus (BE) remains controversial as some studies have shown that the risk of progression to esophageal adenocarcinoma (EAC) is similar for non-goblet cell metaplasia (NGM) and IM. IM harbors genomic aberrations in known cancer-associated genes and these have been linked to increased EAC risk. No detailed studies have explored DNA alterations in NGM. We hypothesized that a comparison of DNA alterations in cancer-associated genes in IM and NGM samples would provide insight into their relative risks for progression to EAC.  Patient biopsies were analyzed using Affymetrix SNP 6.0 arrays, FISH, and targeted resequencing of 20 frequently mutated EAC genes. Frequent CNA’s targeting cancer-associated genes were found in IM whereas no such changes were observed in NGM. In one subject, FISH confirmed loss of CDKN2A and amplification of chromosome 8 in IM but not in a nearby NGM biopsy.  Targeted sequencing in a subset of metaplasia tissues revealed 11 non-synonymous mutations in 16 IM samples and 2 mutations in 19 NGM samples. Our results show that IM has a much higher frequency of cancer-associated mutations than NGM and is therefore likely to pose a higher risk for development of EAC.

overall_design: 57 non-goblet metaplasia, intestinal metaplasias, and composite specimens from 45 subjects were studied. DNA copy number abnormalities (CNA’s) were identified using Affymetrix arrays and fluorescence in situ hybridization (FISH). Data was processed in Nexus 6.0 (BioDiscovery, CA). Targeted sequencing of all exons from twenty genes found to be frequently mutated in EAC was performed on metaplasia samples using Ion AmpliSeq™ DNA sequencing.

last: Peters

first: David

last: Ruff

first: Shiaw-Min

first: Chieh-Yuan

last: Li

first: Kunchang

last: Song

first: Kimberly

last: Thoms

first: Virginia

last: Litle

first: Thomas

last: Watson

first: Nikita

last: Chapurin

first: Michal

last: Lada

first: Arjun

last: Pennathur

first: James

last: Luketich

first: Derick

last: Peterson

first: Austin

last: Dulak

first: Lin

first: Adam

last: Bass

middle: G

last: Beer

first: Tony

last: Godfrey

first: Zhongren

last: Zhou


title: Impact of Ino-C2-PAF on the gene expression profile of HaCaT cells after stimulation with pro-inflammatory cytokines

first: Geo

last: Semini

address: Oudenarderstrasse 16

department: Institute for Biochemie

institute: Charité - Universitätmedizin

summary: New alkyl-phospholipids (APLs) that are structurally derived from the platelet-activating factor are promising candidates for anticancer treatment. After the incorporation into cell membranes, APLs are able to interfere with a wide variety of key enzymes implicated in cell growth, motility, invasion and apoptosis.   Recently, using Agilent cDNA microarray technology, we could demonstrate that the glycosidated APL Ino-C2-PAF inhibited the expression of several genes associated with immune response and inflammation in immortalized keratinocytes HaCaT. Here, we analyzed the impact of Ino-C2-PAF on the gene expression profile of HaCaT cells treated with several pro-inflammatory cytokines (IL-1α, IL-17, IL-22, TNF-α and oncostatin-M).

overall_design: The influence of Ino-C2-PAF on the transcriptional profile of immortalized keratinocytes (HaCaT) was analyzed treating HaCaT cells with 5 µM Ino-C2-PAF in the presence of a mixture of pro-inflammatory cytokines (IL-1α, IL-17, IL-22, TNF-α and oncostatin-M) for 24 h. Control cells were left untreated. Three independent experiments were performed for each condition, except for control cells where only two experiments were performed. Control cells were mainly necessary to demonstrate the efficiency of this in vitro inflammation model for keratinocytes.

first: Andreas

last: Klein

first: Lothar

last: Lucka

first: Kerstin

last: Danker


title: Transcription profiling of major depression peripheral blood mononuclear cells (PBMCs) at clinical remission compared to severe acute state

status: Public on Dec 20 2012

city: MARSEILLE

first: El Chérif

last: Ibrahim

address: 27 Bd Jean Moulin

institute: Aix Marseille Université-CNRS

summary:
PBMCs from major depressive episode (MDE) subjects were obtained at two time points: during a severe episode of depression and eight week later after clinical remission. PBMCs from sex- and age-machted controls were also obtained at an eight weeks interval.
PBMC total RNAs from MDE and control subjects were profiled after hybridization with Agilent SurePrint G3 Human GE 8x60K Microarray to identify blood biomarkers of MDE.

overall_design: Total RNAs were extracted from 36 samples including: 9 control and 9 MDE subjects at two point of time (first and eight week later)

first: Aurélie

last: Bergon

first: Raoul

last: Belzeaux

first: Béatrice

last: Loriod

first: Valérie

last: Jeanjean

first: Lore

last: Verrier

first: ElChérif


title: Differential analysis of HOXA1 in adult cells at isoform resolution by RNA-Seq [Agilent]

status: Public on Dec 11 2012

city: Cambridge

first: Cole

last: Trapnell

address: 7 Divinity Ave

department: Stem Cell and Regenerative Biology

institute: Harvard University

summary: High-throughput RNA sequencing (RNA-Seq) has enabled accurate gene discovery and expression estimation, but robust differential analysis of gene and transcript abundances has proven difficult. We present a new algorithm, implemented in the freely available tool Cuffdiff, which integrates transcript-level expression estimation with a method to control for variability across replicate samples. Cuffdiff robustly identifies differentially regulated isoforms and genes and reveals differential splicing or promoter-preference changes. We demonstrate the accuracy of our approach through differential analysis of lung fibroblasts in response to loss of the developmental transcription factor HOXA1 and uncover a critical role for this gene in the maintenance of adult cells. We show that HOXA1 is required for lung fibroblast and HeLa cell cycle progression, and loss of HOXA1 results in significant expression level changes in thousands of individual transcripts, along with isoform switching events in key regulators of the cell cycle.

overall_design: Lung Fibroblasts were transfected with either a HOXA1 directed siRNA pool or a scramble non-targeting siRNA control. RNA was collected 48 hours after transfection and changes in gene expression were assayed for using Agilent microarrays.

first: David

last: Hendrickson

first: Martin

last: Sauvageau

first: John

last: Rinn

first: Lior

last: Pachter


title: Gene expression signatures in a human bladder cancer cell line SW780 transfected with miR-137 precursor molecule

status: Public on Dec 01 2012

city: Sapporo

first: Hiromu

last: Suzuki

state: Hokkaido

address: S1, W17, Chuo-ku

department: Department of Molecular Biology

institute: Sapporo Medical University

summary: To clarify the effect of miRNAs, we carried out a gene expression microarray analysis of SW780 cells transfected with a miR-137 precursor or a negative control.  We found that 1,326 probe sets (1,016 unique genes) were downregulated (>2-fold) by ectopic miR-137 expression, including the previously reported miR-137 target genes CDK6, CDC42 and AURKA.  Moreover, Gene Ontology analysis revealed that genes related to the cell cycle were significantly enriched among the affected genes.

overall_design: SW780 cells were transfected with a Pre-miR-137 miRNA Precursor Molecule (Ambion) or Pre-miR miRNA Molecules Negative Control #1 (Ambion). Forty-eight hours after transfection, total RNA extraction was carried out, and gene expression signatures were analyzed.

first: Takashi

last: Shimizu


title: Cetuximab resistant or sensitive head and neck cancer samples

city: Linkoping

first: Fredrik

last: Jerhammar

country: Sweden

institute: Linkoping University

summary: 10 cell lines (five cetuximab sensitive and five cetuximab resistant) were selected for gene copy number array analysis on the Affymetrix SNP 6.0 platform. 39 protein coding genes were amplified in cetuximab resistant cells and normal in sensitive cells, all present on genomic regions 11q22.1 or 5p13-15. Five genes were selected for quantitative PCR verification, namely, YAP1 and TRPC6 (11q22.1) and PDCD6, TPPP, and PTGER4 (5p13-15). An extended panel of totally 10 cetuximab resistant and 10 sensitive cell lines verified that YAP1 amplified cells are cetuximab resistant.   YAP1 gene amplification was highly correlated to the YAP1 mRNA expression, which was significantly higher in cetuximab resistant cells than in sensitive. YAP1 downregulation resulted in increased cetuximab sensitivity in one of two cetuximab resistant cell lines investigated and growth inhibition in another. We conclude that YAP1 is a marker for cetuximab resistance in head and neck cancer.

overall_design: head and neck cancer cell lines with established cetuximab response were selected. 5 cetuximab resistant cell lines and 5 cetuximab sensitive cell lines were selected for gene genome wide gene copy number analysis on the Affymetrix SNP6.0 array

first: Karin

last: Roberg


title: Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma [DNA copy number]

status: Public on Dec 06 2012

city: Oslo

first: Leonardo

middle: A.

last: Meza-Zepeda

address: Ullernchausseen 70

department: Dept. of Tumor Biology

country: Norway

institute: The Norwegian Radium Hospital

summary: Osteosarcomas are the most common primary malignant tumours of bone, and almost all conventional osteosarcomas are high-grade tumours showing complex genomic aberrations. We have integrated genome-wide genetic and epigenetic profiles from the EuroBoNeT panel of 19 human osteosarcoma cell lines based on microarray technologies. The cell lines showed complex patterns of DNA copy number changes, where copy number gains were significantly associated with gene-rich regions of the genome and losses with gene-poor areas. Integration of the datasets showed that the mRNA levels were regulated by either alterations in DNA copy number or DNA methylation. Using a recurrence threshold of 6/19 (> 30 %) cell lines, 348 genes were identified as having alterations of two data types (gain or hypo-methylation/over-expression, loss or hyper-methylation/under-expression). These genes are involved in embryonic skeletal system development and morphogenesis, as well as remodelling of extracellular matrix. Several genes were hyper-methylated and under-expressed compared to normal osteoblasts, and expression could be reactivated by demethylation using 5-Aza-2’-deoxycytidine treatment for all four genes tested. Globally, there was as expected a significant positive association between gain and over-expression, loss and under-expression as well as hyper-methylation and under-expression, but gain was also associated with hyper-methylation and under-expression, suggesting that hyper-methylation may oppose the effects of increased copy number for some genes. Integrative analysis of genome-wide genetic and epigenetic alterations identified mechanistic dependencies and relationships between DNA copy number and DNA methylation in terms of regulating mRNA expression levels in osteosarcomas, contributing to better understanding of osteosarcoma biology.

overall_design: Comparison of DNA copy number changes in 19 osteosarcoma cell lines

first: Stine

last: Kresse

first: Halfdan

last: Rydbeck

first: Magne

last: Skårn

first: Heidi

last: Namløs

first: Ana

last: Barragan-Polania

first: Anne-Marie

last: Cleton-Jansen

first: Knut

last: Liestøl

first: Eivind

last: Hovig

first: Ola

last: Myklebost


title: GeneChip Mapping 500K set and Genome-Wide Human SNP 6.0 Array for glioblastomas

status: Public on Nov 30 2012

city: Salamanca

first: MariaDolores

last: Tabernero

address: Paseo San Vicente 58-182

institute: Hospital Universitario de Salamanca y Centro del Cáncer

summary: High-density single nucleotide polymorphism (SNP) arrays were used to investigate genome-wide copy number (CN) alterations and loss of heterozygosity (LOH) in  glioblastomas (GBM) patients; our aim focused on the identification and detailed characterization of the genetic alterations of the chromosomes altered in these tumors and the identification of subgroups of GBM  with distinct cytogenetic patterns of alteration for the affected chromosomes potentially associated with the behavior of the disease. Overall, gains of chromosome 7,  losses of chromosomes 9p and 10 were the most frequent chromosomal alterations. The 7p11.2 region was amplified in several cases. Based on CN alterations for chromosomes 7, 9 and 10, five different cytogenetic patterns with a significant impact on patient survival  were identified; noteworthy, cases with EGFR amplification  showed a better survival, specifically among patients older than 60 years. In addition, our results provide further evidence about the relevance of the EGFR, CDKN2A/B, MTAP genes, and other genes coded in chromosome 10 in the pathogenesis of GBM.  Altogether, our results confirm the cytogenetic heterogeneity of GBM and suggest that stratification of these tumors into genetic subsets based on the combined assessment of cytogenetic alterations involving chromosomes 7, 9 and 10, may contribute to the prognostic evaluation of GBM.

overall_design: GeneChip Mapping 500K set and Genome Wide Human SNP 6.0 Array were used to profile GBM with matched blood DNA samples. Loss of heterozygosity (LOH) and copy number abnormality (CNA) profiles were derived from each tumour-blood pair.

first: Maria

first: Jose

last: Orfao


title: GeneChip Mapping 500K set and Genome-Wide Human SNP 6.0 Array in meningioma tumors

summary: Cytogenetic profiles of 50 meningiomas using high-density GeneChip Mapping 500K set and Genome-Wide Human SNP 6.0 Array in the tumor tissues and in the peripheral blood of the same patients. A total of two hundred 500k arrays (100 tumor samples and 100 blood samples) and 14 SNP6.0 arrays  (7 tumour samples and 7 peripheral blood samples) were studied  to explore the most common recurrent chromosomal abnormalities (gains and losses) in meningiomas. Our results confirm that del(22q) (52%) and del(1p) (16%) (common deleted regions: 22q11.21-22q13.3. and 1p31.2-p36.33) are the most frequent abnormalities.  Additionally, recurrent monosomy 14 (8%), del(6p) (10%), del(7p) (10%) and del(19p) (6%) were also observed, while copy number variation (CNV) patterns consistent with recurrent chromosome gains, gene amplification was absent or rare. Based on their overall SNP profiles meningiomas could be classified into: i) diploid cases, ii) meningiomas with a single chromosome change (e.g. monosomy 22/del(22q) and iii) tumours with ≥2 altered chromosomes.

overall_design: 500K SNP mapping set array and Genome-Wide Human SNP 6.0 Array were used to profile 50 meningiomas with matched blood DNA samples. Loss of heterozygosity (LOH) and copy number abnormality (CNA) profiles were derived from each tumour-blood pair. In seven tumors, both types of arrays were assessed.


title: Performance Comparison of the Affymetrix SNP6.0 and Cytogenetic 2.7M Whole-genome Microarrays in Complex Cancer Samples

status: Public on Nov 26 2012

city: Aalborg

first: Julie

middle: Støve

last: Bødker

address: Sdr. Skovvej 15

department: Department of Heamatology

country: Denmark

institute: Aalborg University Hospital

summary:
We performed a comparison analysis of the Affymetrix arrays SNP6.0 genome wide array (SNP6.0) and cytogenetic 2.7M whole-genome array (Cyto2.7M) using nine human samples. We compared the two array types with respect to four parameters including the size and breakpoints of the alterations detected, the actual CN assigned to the CNVs as well as long stretches of loss of heterozygosity. Overall, we found very good consistency between the two types of array on all parameters compared, even in regions with very complex changes.

This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series

first: Claus

last: Gyrup

first: Preben

last: Johansen

first: Alexander

last: Schmitz

first: Jakob

last: Madsen

first: Hans

last: Johnsen

first: Martin

last: Boegsted

first: Karen

last: Dybkær

first: Mette

last: Nyegaard


title: Affymetrix SNP array data for hepatocellular carcinoma tissue

status: Public on Oct 26 2012

city: Shanghai

first: jie

last: hu

address: 180 Fenglin Road

country: China

institute: Zhongshan hospital, Fudan University

summary: Genetic variations play an important role in tumor development and metastasis. Hepatocellular carcinoma (HCC) is one of leading cause of cancer-related death. Despite improvements in surveillance and clinical treatment strategies, the prognosis of HCC remains dismal. Affymetrix SNP 6.0 array were used to evaluate the genetic characteristics of tumor DNA in 30 HBV-related HCC patients who were underwent liver transplantation. Recurrence related SNPs were selected and validated.

overall_design: Affymetrix SNP 6.0 arrays were performed according to the manufacturer's directions on DNA extracted from formalin-fixed paraffin-embedded HCC tissues

first: Jian

last: Zhou

first: Jie

last: Hu

first: Zheng

last: Wang


title: Gene expression profiles of head and neck squamous cell carcinoma and renal cell carcinoma

status: Public on Nov 12 2012

city: Chiba

first: Naohiko

last: Seki

state: Chiba

address: 1-8-1 Inohana,Chuo-ku

department: School of Medicine

institute: Chiba University

summary: To identify differentially expressed genes in tumor tissues, several human cancer tissues (hypopharyngeal squamous cell carcinoma, maxillary sinus squamous cell carcinoma, and renal cell carcinoma) were subjected to Agilent whole genome microarrays.

overall_design: A total of nine pairs of primary hypopharyngeal squamous cell carcinoma samples and adjacent normal mucosa were obtained from patients who underwent tumor resection at Chiba University Hospital (Chiba, Japan). A total of seven pairs of primary maxillary sinus squamous cell carcinoma samples and adjacent normal mucosa were obtained from patients who underwent tumor resection at Chiba University Hospital (Chiba, Japan). A total of five pairs of renal cell carcinoma samples and adjacent normal tissues were obtained from patients who underwent tumor resection at Kagoshima University Hospital (Kagoshima, Japan). The Ethics Committee of Chiba University and the Bioethics Committee of Kagoshima University approved our study, and informed consent was obtained from all patients for use of their tissue samples and clinical data. The tissue samples were immediately frozen in liquid nitrogen and stored at -80°C until use.


title: The histotype-specific copy-number landscape of ovarian cancer (copy number SNP)

status: Public on Oct 25 2012

city: Singapore

first: Liang

last: Goh

address: College Road

country: Singapore

institute: Duke-NUS graduate medical school

summary: Ovarian cancer is characterized by multiple structural aberrations; most are passenger alterations which do not confer tumor growth.  Like many cancers, it is a heterogeneous disease and till date, the histotype-specific copy number landscape has been difficult to elucidate.  To dissect the heterogeneity of ovarian cancer and understand the pathogenesis of its various histotypes, we developed an in silico hypothesis-driven workflow to identify histotype-specific copy number aberrations across multiple datasets of epithelial ovarian cancer.  In concordance with previous studies on global copy number changes, our study showed similar alterations.  However, when the landscape was de-convoluted into histotypes, distinct alterations were observed.  We report here a comprehensive histotype-specific copy number landscape of ovarian cancer and showed that there is genomic diversity between the histotypes; some involving well known cancer genes and some novel potential driver genes.  Besides preferential occurrence of alterations in some histotypes, opposite trends of alteration were observed; such as ERBB2 amplification in mucinous but deletion in serous tumors.  The landscape highlights the need for identifying histotype-specific aberrations in ovarian cancer and present potential to tailor management of ovarian cancer based on molecular signature of histotypes.

overall_design:
46 archived frozen tumor samples collected from Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taiwan, containing 9 clear cell, 6 mucinous, and 31 serous.
Data was pre-processed and normalized with Hapmap CHB using the Affymetric Genotyping Console.


title: The histotype-specific copy-number landscape of ovarian cancer (copy number Japan)

overall_design:
56 samples containing the 4 histotypes were used for this study.  It contained 12 clear cell carcinoma, 6 endometrioid adenocarcinoma, 2 mucinous adenocarcinoma, 5 mucinous-borderline tumors, 26 serous adenocarcinoma, and 5 serous-borderline tumors.
Data was pre-processed and normalized with Hapmap JPT using the Affymetric Genotyping Console.


title: SNP6.0 copy number analysis of eight diffuse large B-cell samples and one matched blood sample

summary: We performed a comparison analysis of the Affymetrix arrays SNP6.0 genome wide array (SNP6.0) and cytogenetic 2.7M whole-genome array (Cyto2.7M) using nine human samples. We compared the two array types with respect to four parameters including the size and breakpoints of the alterations detected, the actual CN assigned to the CNVs as well as long stretches of loss of heterozygosity. Overall, we found very good consistency between the two types of array on all parameters compared, even in regions with very complex changes. This GEO submission contains the SNP6.0 data. GEO submission, GSE37978 contains the Cyto2.7M data.

overall_design:
DNA was extracted from eight samples of diffuse-large B-cell lymphoma with complex genomic rearrangements using the DNeasy Blood & Tissue kit (Qiagen) following manufactures instructions. DNA was also included from one matched blood sample where mononuclear cells were isolated from the blood sample by Ficoll-Paque Plus (GE Health Care, Uppsala, Sweden) and stored in 10 % DMSO and 20 % serum at – 80 oC. For DNA extraction, the cells were thawed, washed twice in PBS and genomic DNA extracted using the DNeasy Blood & Tissue kit (Qiagen). The DNA was eluted in water and the concentration measured using a Nanodrop (Thermo Scientific).
Copy number analysis of Affymetrix SNP6.0 arrays was performed on eight diffuse large B-cell samples and one matched blood sample.


title: High-Resolution Genomic Profiling of Chronic Lymphocytic Leukemia Reveals New Recurrent Genomic Alterations

status: Public on Oct 11 2012

city: Ulm

first: Karlheinz

last: Holzmann

address: Helmholtzstreet 8/1

institute: Ulm University

summary: To identify genomic alterations in chronic lymphocytic leukemia (CLL), we performed single-nucleotide polymorphism (SNP)-array analysis on 353 samples from previously untreated patients entered on the CLL8 treatment trial. Based on paired-sample analysis (n=147), a mean of 1.8 copy number alterations (CNAs) per case were identified; about 60% of cases carried no CNAs other than those detected by routine fluorescence in-situ hybridization analysis. Copy-neutral loss-of- heterozygosity was detected in 6% of cases, and most frequently found on 13q, 17p and 11q. Minimal deleted regions (MDRs) were refined on 13q14 (deleted in 61% of cases) to the DLEU1 and DLEU2 genes, on 11q22.3 (27%) to ATM, on 2p (gained in 7% of cases) to a 1.9 Mb fragment containing 9 genes, and on 8q24 (5%) to a segment 486 Kb proximal of the MYC locus. 13q deletions exhibited proximal and distal breakpoint cluster regions. Among the most common novel lesions were deletions at 15q15.1 (4%), with the smallest deletion (70.5 Kb) found in the MGA locus; sequence analysis of MGA in 59 samples revealed a truncating mutation in one case lacking a 15q deletion. MNT at 17p13.3, which in addition to MGA and MYC encodes for the network of MAX-interacting proteins, was also found recurrently deleted.

overall_design: Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic peripheral blood samples. Copy number analysis of Affymetrix® performed for 353 CLL samples. There are also 147 samples from mononuclear cells negative for CD19, which were used as references for copy number inference.

first: Jennifer

last: Edelmann


title: Global gene expression profile of coronary artery disease in Asian Indians

status: Public on Nov 09 2012

city: Bangalore

first: prathima

last: arvind

address: #258/A, Bommasandra Industrial Area, Anekal Taluk

department: Functional Genomics

country: India

institute: Thrombosis Research Institute

summary: Global gene expression profile of whole blood in patients with coronary artery disease (CAD) showed significant upregulation of 343 genes and down regulation of 151 genes as compared to controls (p<0.05). There was predominant differential regulation of inflammatory and immune response genes as well as early growth response genes in our dataset. Of the ten candidate genes selected for validation by real time PCR in an independent cohort, CXCL1, EGR3, IL8, PTGS2 and CD69 genes were up regulated and IFNG and FASLG down regulated in cases relative to controls.

overall_design: We selected 13 patients with angiographically confirmed coronary artery disease (CAD) between ages 40 - 55 years and 11 population-based asymptomatic controls with normal ECG and matched for age, gendre and common risk factors such as diabetes and hypertension to that of the cases. Global gene expression profiling was performed on the Agilent microarray platform.

first: Prathima

last: Arvind

first: Jayashree

last: Shanker


title: Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma.

first: Leonardo

last: Meza-Zepeda

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

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

first: Stine

last: Kresse

first: Halfdan

last: Rydbeck

first: Magne

last: Skårn

first: Heidi

last: Namløs

first: Ana

last: Barragan-Polania

first: Anne-Marie

last: Cleton-Jansen

first: Knut

last: Liestøl

first: Eivind

last: Hovig

first: Ola

last: Myklebost


title: Integrated Genetic and Epigenetic Analysis of Childhood Acute Lymphoblastic Leukemia Reveals a Synergistic Role for Structural and Epigenetic Lesions In Determining Disease Phenotype

status: Public on Dec 12 2012

city: Memphis

first: Charles

last: Mullighan

address: 262 Danny Thomas Place

department: Pathology

institute: St Jude Children's Research Hospital

summary: Acute lymphoblastic leukemia (ALL), the commonest childhood malignancy, is characterized by recurring gross and submicroscopic structural genetic alterations that contribute to leukemogenesis. Disordered epigenetic regulation is a hallmark of many tumors, and while analysis of DNA methylation of limited numbers of genes or ALL samples suggests epigenetic alterations may also be important, a large-scale integrative genome-wide analysis evaluating DNA methylation in ALL has not been performed. Here, we report an integrated epigenomic, transcriptional and genetic analysis of 167 childhood ALL cases, comprising B-progenitor ALL with hyperdiploidy (N=26), ETV6-RUNX1 (N=27), TCF3-PBX1 (N=9), BCR-ABL1 (N=19), rearrangement of MLL (MLLr) (N=20), rearrangement of CRLF2 (N=11, CRLF2r), deletion of ERG (N=11), miscellaneous or normal karyotype (N=14), and T-lineage ALL (N=30), including 4 MLLr cases and 7 cases with early T-cell precursor immunophenotype. Genome-wide profiling of structural DNA alterations was performed for all cases using Affymetrix 500K and SNP 6.0 arrays. Affymetrix U133A gene expression profiling data was available for 154 cases. Genome-wide methylation profiling was performed using the HELP microarray assay, which measures methylation at approximately 50,000 CpGs distributed among 22,722 Refseq promoters. Methylation data was compared to that of normal pro-B (CD34+CD19+sIg-), pre-B (CD34-CD19+sIg-) and mature B (CD34-CD19+sIg+) cells FACS-sorted from bone marrow of 6 healthy individuals. Unsupervised hierarchical clustering of the top 4043 most variable methylation probesets identified 9 B-ALL clusters with significant correlation to specific genetic lesions including ETV6-RUNX1, MLLr, BCR-ABL1, CRLF2r, TCF3-PBX1 and ERG deletion.  T-ALLs and hyperdiploid B-ALLs also defined specific DNA methylation clusters.  Supervised analysis including limma and ANOVA identified distinct DNA methylation signatures for each subtype. Notably, the strength of these signatures was subtype dependent, with more differentially methylated genes observed in ALL cases with genetic alterations targeting transcriptional regulators (e.g. ETV6-RUNX1 and MLLr) and fewer genes in cases with alterations deregulating cytokine receptor signaling (e.g. CRLF2r). Aberrant DNA methylation affected specific and distinct biological processes in the various leukemia subtypes implicating epigenetic regulation of these pathways in the pathogenesis of these different forms of ALL (e.g. TGFB and TNF in ERG deleted leukemias; telomere and centriole regulation in BCR-ABL1 ALL).  Aberrantly methylated genes were also enriched for binding sites of known or suspected oncogenic transcription factors that might represent cooperative influences in establishing the phenotype of the various B-ALL subtypes. Most importantly, an integrated analysis of methylation and gene expression of these ALL subtypes demonstrated striking inversely correlated expression of the corresponding gene transcripts.   The methylation signatures of each subtype exhibited only partial overlap with those of normal B cells, indicating that the signatures do not simply reflect stage of lymphoid maturation. In a separate approach, we discovered that 81 genes showed consistent aberrant methylation across all ALL subtypes, including the tumor suppressor PDZD2, HOXA5, HOXA6 and MSH2. Inverse correlation with expression was confirmed in 66% of these genes.  These data suggest the existence of a common epigenetic pathway underlying the malignant transformation of lymphoid precursor cells. Integrative genetic and epigenetic analysis revealed hypermethylation of genes on trisomic chromosomes that do not show increased expression, suggesting that epigenetic silencing may control genes within amplified regions and explain why only selected genes are overexpressed. Finally, analysis of individual genes targeted by recurring copy number alterations in ALL revealed a subset of genes also targeted by abnormal methylation, with corresponding changes in gene expression (e.g. ERG, GAB1), suggesting that such genes are inactivated far more frequently than suggested by genetic analyses alone.  Collectively, the data support a key role of epigenetic gene regulation in the pathogenesis of ALL, and point towards a scenario where genetic and epigenetic lesions cooperatively determine disease phenotype.

overall_design:
154 Diagnostic ALL samples were analyzed. There are no replicates.
This GEO submission contains only the U133A gene expression profile data described in the study summary.

first: Maria

last: Figueroa

first: Shann-Ching

last: Chen

first: Anna

middle: K

last: Andersson

first: Wei

last: Liu

first: Cheng

last: Cheng

first: Letha

last: Phillips

first: Yushan

last: Li

first: James

last: Downing

first: Ari

last: Melnick


title: Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

first: Joanna

middle: Dawn

last: Holbrook

address: 30 Medical Drive

institute: Singapore Institute of Clinical Sciences

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


title: COLO320 DNA copy number analysis

status: Public on Nov 02 2012

city: Boston

first: Keyan

last: Salari

address: Gray/Bigelow Rm 1102, 55 Fruit Street

institute: Massachusetts General Hospital

summary: Somatic DNA alteration underlies tumor development and progression, and gives rise to tumors with diverse genetic contexts. Here, we identify in a collection of 29 colorectal cancer cell lines and 226 primary colorectal tumors recurrent amplification of chromosome 13, an alteration highly restricted to colorectal-derived cancers. A minimal region of amplification on 13q12.2 pinpoints caudal type homeobox transcription factor CDX2, a master regulator of anterior-posterior patterning, midgut development, and intestinal epithelial cell differentiation and maintenance. In contrast to its described role as a colorectal tumor suppressor, we show that in the context of genomic amplification, CDX2 is required for proliferation and anchorage-independent growth of colorectal cancer cells. By genome-wide expression and location analysis, we reveal that CDX2 directly promotes expression of Wnt pathway genes. Further results suggest that CDX2 induces expression of intestinal differentiation markers and modulates b-catenin transcriptional activity. These data characterize CDX2 as a novel lineage-survival oncogene deregulated in colorectal cancer.

overall_design: Genome-wide DNA copy number analysis of cell line COLO320 by Affymetrix SNP 6.0 array

first: Jonathan

middle: R

last: Pollack


title: Human monocyte-derived DCs: effect of IL-4 superkines

status: Public on Sep 21 2012

city: Stanford

first: Remi

last: Creusot

state: CA

address: 269 Campus Dr, CCSR 2240

institute: Stanford University

summary: Gene expression induced by IL-4 and IL-4 superkines on CD14+ monocytes cultured in the presence of GM-CSF. Super-4 and KFR signal preferentially through the type I and type II IL-4 receptor, respectively.

overall_design: Five biological replicates (n=5 healthy donors), four conditions: GM-CSF alone or in combination with IL-4, Super-4 or KFR. Two colors: Cy3 for GM-CSF alone, Cy5 for any combination. Cells were cultured for 6 hours with 50 ng/ml of GM-CSF and 20 ng/ml of IL-4, Super-4 or KFR.

first: Ignacio

last: Moraga

first: C

last: Fathman

first: K

last: Garcia


title: Affymetrix SNP array data for acute myeloid leukemia (AML) samples with complex karyotype

status: Public on Aug 27 2012

first: Frank

middle: G.

last: Ruecker

address: Albert-Einstein-Allee 23

department: Internal Medicine III

institute: University of Ulm

summary: AML with complex karyotype (CK-AML) is characterized by a high frequency of TP53 alteration (loss and/or mutation). TP53-altered CK-AML were characterized by a higher degree of genomic complexity (aberrations per case, 14.30 vs. 6.16; P<.0001), and by a higher frequency of specific copy number alterations, such as -5/5q-, -7/7q-, -16/16q-, -18/18q-, +1/+1p, and +11/+11q/amp11q13~25; among CK-AML, TP53-altered more frequently exhibited a monosomal karyotype (MK). Patients with TP53 alterations were older and had significantly lower complete remission rates, inferior event-free, relapse-free, and overall survival. In multivariable analysis for overall survival, TP53 alterations, white blood cell counts, and age were the only significant factors. In conclusion, TP53 is the most frequently known altered gene in CK-AML. TP53 alterations are associated with older age, genomic complexity, specific DNA copy number alterations, MK, and dismal outcome. In multivariable analysis, TP53 alteration is the most important prognostic factor in CK-AML, outweighing all other variables, including the MK category.

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.

first: Rücker

last: Frank


title: A framework for identification of actionable cancer genome dependencies in small cell lung cancer

city: Cologne

first: Felix

last: Dietlein

state: NRW

address: Weyertal 115b

department: Department of Translational Genomics

institute: University of Cologne

summary:
We analyzed copy numbers of 60 SCLC cell lines using 6.0 SNP-arrays. For a subgroup of 36 cell lines, previously published copy number data was utilized.
CEL and SEG files are included for all cell lines, for which copy number data were not publicly available.

overall_design: DNA was extracted from SCLC cell lines and copy number data was generated for all samples

first: Martin

last: Sos

first: Roman

last: Thomas


title: Affymetrix SNP 6.0 array data for colon, gastric and esophageal adenocarcinoma cancer types

status: Public on Sep 04 2012

first: Steven

middle: E

last: Schumacher

address: 450 Brookline Ave

department: Cancer Biology

institute: Dana-Farber Cancer Institute

summary: Using data from high-density genomic profiling arrays, we describe the profiles of somatic copy-number aberrations (SCNAs) in 486 adenocarcinomas across all three major digestive organs, including 296 gastric and esophageal cancers. This analysis revealed that although patterns of broad, chromosome arm-level alterations are similar across the three types of adenocarcinoma, focal genomic amplifications are substantially more prevalent in gastric/esophageal adenocarcinoma. A statistical analysis identified 64 regions of significantly recurrent amplification and deletion, including those shared across these tumors and those uniquely significant in adenocarcinomas from a single organ.  Among significantly amplified genes are those encoding therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, events noted in 14% of colorectal adenocarcinomas and 37% of gastric/esophageal tumors suggesting that analysis of genomic amplification will be a critical source of biomarkers to guide therapies in upper gastrointestinal adenocarcinomas.  While many of the other significant loci of amplifications implicate genes recognized to play roles in gastrointestinal and other cancers, other loci point to regions that may harbor novel genes contributing to these cancers.  One such event is a recurrent focal deletion present in 15% of esophageal adenocarcinomas, which we narrow to a single likely target, the Runt transcription factor subunit RUNX1. Indeed, reintroduction of RUNX1 into a cell model with this deletion inhibited anchorage-independent growth. Overall, these results demonstrate genomic features common to these tumors and identify key differences that reflect distinctive biology and potential opportunities for therapeutic intervention.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from 271 cancer DNAs derived from primary tissues, as well as from DNA obtained from 60 normal DNA samples.
Signal intensities were normalized to raw copy number estimates using the tangent normalization method, as described in Beroukhim et al., In Press and Mermel et al., In preparation. The SNP 6.0 data from this submission were  segmented using CBS. These segmented data were then combined with segmented Affymetrix 250K Sty data for 128 colon, 13 gastric and 74 esophageal adenocarcinomas using common markers to anchor the segments.  Data analysis across samples was performed using this GISTIC 2.0 algorithm (Mermel C et al, Genome Biology 2011).

first: Austin

last: Dulak

first: Rameen

last: Beroukhim

first: Adam

last: Bass


title: Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine [Affymetrix SNP array data]

summary:
Background: Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries.
Methods: Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers.
Results: Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways.
Conclusions: The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery.

overall_design: DNA and RNA samples were obtained from hospitals in Russia and Vietnam according to IRB approved Protocols and with IRB approved consent forms from which informed consents were given for molecular and genetic analysis. The medical centres themselves also have internal ethical committees with reviewed the protocol and ICFs. The samples were sourced through Tissue Solutions Ltd (http://www.tissue-solutions.com/). Genotypes and copy number profiles were generated for each samples using 1 ug of DNA run on Affymetrix SNP V6 arrays using Affymetrix protocols.


title: Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells

status: Public on Sep 12 2012

city: Martinsried

first: Gabriele

last: Stoehr

address: Am Klopferspitz 18

department: Proteomics ans Signaltransduction

institute: MPI of Biochemistry

summary: Extra chromosome copies markedly alter the physiology of eukaryotic cells, but the underlying reasons are not well understood. We created human trisomic and tetrasomic cell lines and determined the quantitative changes in their genome, transcriptome and proteome in comparison to their diploid counterparts.

overall_design: Aneuploid cell lines derived from HCT116 and RPE-1 cell lines were compared to their diploid counterparts; per study, 3 biological replicates have been performed.

first: Coenen

last: Silvia

first: Stoehr

last: Gabriele

first: Storchova

last: Zuzana


title: Affymetrix SNP 6.0 array data from neuroendocrine primary tumor and its metastasis

status: Public on Jul 17 2012

city: Graz

first: Carina

last: Fischer

address: Stiftingtalstr. 24

country: Austria

institute: ZMF

summary:
Reports on common mutations in neuroendocrine tumors (NET) are  rare and clonality of NET metastases has not been investigated in this tumor entity  yet. We selected a NET and a the corresponding lymph node and liver metastases as  well as the derivative cell lines to screen for somatic mutations in the primary NET  and to track the fate of genetic changes (by Affymetrix SNP 6.0 micorarray and targeted resequencing by 454 GS FLX) and during metastasis and in vitro progression.
using Affymetrix SNP 6.0 Arrays.

overall_design: Affymetrix SNP 6.0 arrays were performed according to the manufacturer's directions on DNA extracted from cryo material or cell lines.  Copy number analysis of Affymetrix SNP 6.0 arrays was performed for 4 samples. 60 samples from HapMap database were used as references for copy number inference.

first: B

last: Rinner

last: Gülly


title: Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome

status: Public on Jul 24 2012

city: Zurich

first: Michael

last: Baudis

address: Winterthurerstrasse 190

department: Institute of Molecular Life Sciences

country: Switzerland

institute: University of Zurich

summary:
Background: Renal cell carcinoma (RCC) is characterized by a number of diverse molecular aberrations that differ among individuals. Recent approaches to molecularly classify RCC were based on clinical, pathological as well as on single molecular parameters. As a consequence, gene expression patterns reflecting the sum of genetic aberrations in individual tumors may not have been recognized. In an attempt to uncover such molecular features in RCC, we used a novel, unbiased and integrative approach.
Methods: We integrated gene expression data from 97 primary RCCs of different pathologic parameters, 15 RCC metastases as well as 34 cancer cell lines for two-way nonsupervised hierarchical clustering using gene groups suggested by the PANTHER Classification System. We depicted the genomic landscape of the resulted tumor groups by means of Single Nuclear Polymorphism (SNP) technology. Finally, the achieved results were immunohistochemically analyzed using a tissue microarray (TMA) composed of 254 RCC. Results: We found robust, genome wide expression signatures, which split RCC into three distinct molecular subgroups. These groups remained stable even if randomly selected gene sets were clustered. Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors. SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. TMA analysis with group-specific markers showed a prognostic significance of the different groups. Conclusion: We propose the existence of characteristic and histologically independent genome-wide expression outputs in RCC with potential biological and clinical relevance.

overall_design: Expression profiling by array, combined data analysis with genomic profiling data. Genomic DNA from renal cell was hybridized to renal cell carcinoma samples and matched normal kidney tissue biopsies, using the Affymetrix GenomewideSNP_6 platform. CEL files were processed using R, Bioconductor and software from the aroma.affymetrix project. Visualized Copy number profiles are accessible through the Progenetix site (www.progenetix.net). CN,raw.csv and segments.csv: Probes are mapped by their position in genome build 36 / HG18. Probes are ordered according to their linear position on the Golden Path.

last: Beleut

first: Holger

last: Moch

first: Peter

last: Schraml

first: Zimmermann

last: Philip


title: Subgroup specific somatic copy number aberrations in the medulloblastoma genome [gDNA]

status: Public on Jul 27 2012

city: HEIDELBERG

first: Paul

last: Northcott

address: Im Neuenheimer Feld 280

institute: German Cancer Research Center (DKFZ)

summary: Affymetrix SNP6 profiling of 1087 medulloblastoma samples and 10 medulloblastoma cell lines.

overall_design: Genomic DNA was extracted from primary medulloblastoma samples and medulloblastoma cell lines and hybridized to Affymetrix SNP6 arrays according to the manufacturer's instructions.

middle: A

first: David

last: Shih

middle: D

last: Taylor


title: Gastrointestinal Adenocarcinomas of the Esophagus, Stomach, and Colon Exhibit Distinct Patterns of Genome Instability and Oncogenesis.

status: Public on Aug 31 2012

last: Schumacher

overall_design: Refer to individual Series

middle: M

last: Dulak

last: Beroukhim


title: Differences in cytokine production in human macrophages and in virulence in mice are attributable to the PA protein of H5N1 influenza viruses

status: Public on Sep 30 2012

city: Obihiro

first: Ryo

last: Takano

address: Inada-cho

department: National Research Center for Protozoan Diseases

country: Japan

institute: Obihiro University of Agriculture and Veterinary Medicine

summary:
Background. The pathogenesis of influenza A virus subtype H5N1 (hearafter, "H5N1") infection in humans is not completely understood, although hypercytokinemia is thought to play a role. We previously reported that most H5N1 viruses induce high cytokine responses in human macrophages, whereas some H5N1 viruses induce only a low level of cytokine production similar to that induced by seasonal viruses.

Methods. To identify the viral molecular determinants for cytokine induction of H5N1 viruses in human macrophages, we generated a series of reassortant viruses between the high cytokine inducer A/Vietnam/UT3028II/03 clone 2 (VN3028IIcl2) and the low inducer A/Indonesia/UT3006/05 (IDN3006), and evaluated cytokine expression in human macrophages.

Results. Viruses possessing the acidic polymerase (PA) gene of VN3028IIcl2 exhibited high levels of hypercytokinemia-related cytokine expression in human macrophages, compared with IDN3006, but showed no substantial differences in viral growth in these cells. Further, the PA gene of VN3028IIcl2 conferred enhanced virulence in mice.

Conclusions. These results demonstrate that the PA gene of VN3028IIcl2 affects cytokine production in human macrophages and virulence in mice. These findings provide new insights into the cytokine-mediated pathogenesis of H5N1 infection in humans.

overall_design: Human monocyte-derived macrophages were mock-infected, or infected with IDN3006, VN3028IIcl2, or IDN3006/cl2PA at a multiplicity of infection (MOI) of 2. At 6 hours post-infection (hpi), the cells were harvested and subjected to microarray analysis (three technical replicates per each group).

first: Saori

last: Sakabe


title: Analysis of the coding exome of follicular lymphoma

status: Public on Jan 17 2014

city: Ann Arbor

first: Sami

middle: N

last: Malek

address: 4410 Cancer Center; 1500 E Medical Center Dr

department: Internal Medicine, Hematology-Oncology

country: USA

institute: University of Michigan

summary: Follicular lymphoma (FL) constitutes the second most common non-Hodgkin lymphoma in the Western world.  FL carries characteristic recurrent structural genomic aberrations. However, information regarding the coding genome in FL is still evolving. Here, we describe the results of massively parallel exome sequencing and high-resolution SNP 6.0 array profiling of 12 highly purified FL cases and validation of mutations in an expansion cohort of 45 cases. In addition to confirming high-frequency mutations in MLL2, CREBBP and BCL2, we report identification of 18 recurrently mutated genes in FL. These include novel mutations in MCL1, IRF8 and POU2FA/OCT2, and high-frequency mutations in various components of the linker histone HIST1H1. Further, multiple novel mutated genes located within regions of acquired uniparental disomy (aUPD) are identified, providing candidate genes for this common lesion type in FL. In aggregate, these data substantially broaden our understanding of the types and frequency of recurrently mutated genes and pathways in FL

overall_design: Twelve paired normal and tumor follicular lymphoma cases were profiled by SNP array for this study.  However, in addition the data from 125 CEL files derived from the DNA of flow-sorted CD3+ cells from 125 CLL patients (122 CEL files from GSE30777) were used to firmly establish a normal copy number baseline for the dChip software to compute all subsequent normal and tumor DNA copy number values.

first: Mark

last: Kaminski

first: Yifeng

last: Li

first: Hongxiu

last: Ouillette

first: Siân

last: Jones

first: Heather

last: Fox

first: Kathryn

last: Jacobi

first: Kamlai

last: Saiya-Cork

first: Dale

last: Bixby

first: Daniel

last: Lebovic

first: Kerby

last: Shedden

last: Sabel

first: Lawrence

last: Marentette

first: Vincent

last: Cimmino

first: Alfred

last: Chang


title: The histotype-specific copy-number landscape of ovarian cancer

first: Liang

last: Goh


title: AUTS2 project

status: Public on Jul 12 2012

city: Amsterdam

first: Els

last: Voorhoeve

address: De Boelelaan 1117

department: Clinical Genetics

country: Netherlands

institute: VU medical center


title: Affymetrix SNP 6.0 array data for chordoma samples

first: Carina

last: Fischer

summary: Chordomas are rare, low to intermediate grade malignant bone tumors of the axial skeleton, believed to originate from the notochord. Treatment options are limited and mainly restricted to surgical excision, as chordomas have been proven to be largely resistant to conventional ionizing radiation and chemotherapy. Therefore a new cell line was established. The cell line has been characterized by immunohistochemistry,western blot and karyotyping using cobra fish technology. Copy number variations (CNV) and loss-of heterozygosity (LOH) from fibroblasts, tumor tissue, low and high cell line passage was evaluted by using Affymetrix 6.0SNP Arrays. DNA isolated from the patients MNCs was used as control. The cell line MUG-Chor1 is highly similar to genetic profiles of chordomas and provides therefore a powerful tool for further investigations.

overall_design:
Affymetrix SNP 6.0 arrays were performed according to the manufacturer's directions on DNA extracted from cryo material or cell lines.
Copy number analysis of Affymetrix SNP 6.0 arrays was performed for 4 samples. 60 samples from HapMap database were used as references for copy number inference.

first: Beate

last: Rinner

first: Chrisitan

last: Gülly


title: Affymetrix SNP array data for a melanoma lesion and a cellline derived thereof

status: Public on Jun 18 2012

city: Vienna

first: Mario

last: Mikula

address: Waehringergürtel 18-20

department: General Dermatology

institute: Medical University Vienna

summary: Here we report on a bulk culture termed MCM1, which was derived from a 61 year old male diagnosed with a nodular melanoma stage T2a, N0. At passage three of culturing, DNA was isolated and Affymetrix SNP6.0 array hybridizations were performed. Cultured MCM1 cells revealed overall identical copy number gains and losses as compared with the primary patient-derived lesion and were therefore used in this study.

overall_design: Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA, which was extracted from a patient derived melanoma sample and from a cellline generated from the same melanoma sample at passage three.

first: Peter

last: Petzelbauer