title: Genotyping data from one patient with unexplained mental retardation and a deletion in 15q13

status: Public on Mar 05 2011

city: Tuebingen

last: Bonin

address: CAlwerstr. 7

department: Medical Genetics

institute: University Tuebingen

summary: Recurrent deletions on 15q13.3 have been identified as a predisposition to mental retardation, epilepsy and psychiatric disease. We report compound heterozygous deletions on 15q13.3 in one patients with severe encephalopathy and seizures.

overall_design: We analysed two independent patients with severe encephalopathy and seizures and found heterozygous deletions on 15q13.3 in both patients.

first: Karl

last: Hackmann

first: Evelin

last: Schröck

first: Ute

last: Moog


title: Affymetrix SNP6.0 data for human induced pluripotent stem cells (hiPSCs), human Fibroblasts, and human embryonic stem cells (hESCs)

status: Public on Jan 31 2011

city: Toronto

first: Samer

last: Hussein

address: 25 Orde St.

country: Canada

institute: SLRI-Mount Sinai Hosp.

summary: In this study, copy number variations of  hiPSCs were compared to their parental fibroblast lines and hESCs to assess the level of DNA damage incurred due to the process of reprogramming of somatic cells. Higher levels of copy number changes were observed in hiPSCs (especially in early passage hiPSCs) compared to the other cell types.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from in vitro cultured cells.
Copy number analysis of Affymetrix SNP 6.0 arrays was performed for 35 hiPSC samples, 2 hESC samples, and 5 fibroblast samples. Other hESC and the reference Hapmap sample CEL files were obtained from Narva et al. 2010, Nat. Biotech., GEO accession code GSE15097 (see readme file below for details).

first: Andras

last: Nagy


title: Copy number analysis of Hodgkin lymphoma cell lines KM-H2 and L-428

status: Public on Dec 11 2010

city: Vancouver

first: Christian

last: Steidl

state: BC

address: 675 West 10th Avenue

department: Pathology

institute: BC Cancer Agency

summary: We identified copy number changes associated with fusion transcripts and breakpoints on chromosomes 15 and 16.

overall_design: Data integration with RNAseq data

first: Nathalie

last: Johnson

first: Sohrab

middle: P

last: Shah


title: Affymetrix SNP array data for ovarian cancer cells OVCAR-3 and FU-OV-1

status: Public on Dec 24 2010

city: Zurich

first: Jean-Philippe

middle: Paul

last: Theurilllat

address: Schafmattstrasse 18

department: Cell Biology

country: Switzerland

institute: ETH Hönggerberg

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

summary: A subset of ovarian cancer are characterized by 19q12 amplification. To perform funtional studies of this amplicon the profile has been determined by SNP analysis.

overall_design: Affymetrix SNP arrays were performed according to the manufacturer's directions on genomic DNA extracted from ovarian cancer cell lines OVCAR-3 and FU-OV-1

last: Theurillat

first: Stefan

last: Neuenschwander


title: Prospective comparison of genome-wide aCGH platforms for the detection of CNVs in MR

status: Public on Feb 17 2011

first: Tracy

last: Tucker

address: Box 153 4480 Oak Street

institute: University of British Columbia

type: Genome variation profiling by genome tiling array

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

overall_design: Refer to individual Series


title: Genome-wide connection between DNA methylation and DNA replication timing

status: Public on Dec 01 2010

city: Jerusalem

first: Asaf

last: Hellman

address: Hadassah Medical School

department: Developmental Biology and Cancer Research

country: Israel

institute: Hebrew University

summary: DNA methylation and DNA replication timing were examined across a variety of human tissues and cell lines, applying microarray-based techniques. The analyses revealed that late-replicating DNA was demethylated compared to the methylation of early-replicating regions.

overall_design: DNA methylation: Epstein-Barr-Virus (EBV) transformed B-lymphocyte cell lines GM10849, GM12089, GM12092, GM12093, and GM08714 (ICF) (http://ccr.coriell.org/nigms) were cultured in RPMI-1640 supplemented with 15% FCS (Sigma) at 37oC and 5% CO2. Normal BJ foreskin fibroblasts (NHF cells) at different PDs (36)(34) were cultured in 4:1 DMEM : M-199 supplemented with 15% FCS (Sigma) at 37oC and 5% CO2. Replication timing: EBV-transformed female B-lymphocyte cell lines GM12092 and GM12093 were cultured as above, harvested from logarithmic growth cultures, washed once in ice-cold phosphate-buffered saline, immediately fixed in 70-85-95% ethanol at -20oC, stained with propidium iodide, and sorted into G1 and early-S fractions using a MoFlo cell sorter.


title: NF1 inactivation in adult acute myelogenous leukemia

status: Public on Dec 02 2010

city: Ann Arbor

first: Sami

middle: N

last: Malek

state: MI

address: 4410 Cancer Center; 1500 E Medical Center Dr

department: Internal Medicine, Hematology-Oncology

country: USA

institute: University of Michigan

summary:
Purpose: This study was conducted to identify novel genes with importance to the biology of adult acute myelogenous leukemia (AML).

Conclusions: NF1 null states are present in 7/95=7% of adult AML and delineate a disease subset that could be preferentially targeted by Ras or mTOR-directed therapeutics.

overall_design:
Experimental design: We analyzed DNA from highly purified AML blasts and paired buccal cells from 95 patients for recurrent genomic microdeletions using ultra-high density Affymetrix SNP 6.0 array-based genomic profiling.
006, 096 and 136 normal Samples have been excluded from study.

first: Brian

last: Parkin

first: Peter

last: Ouillette

first: Yin

last: Wang

first: Yan

last: Liu

first: Whitney

last: Wright

first: Diane

last: Roulston

first: Anjali

last: Purkayastha

first: Amanda

last: Dressel

first: Judith

last: Karp

first: Paula

last: Bockenstedt

first: Ammar

last: Al-Zoubi

first: Moshe

last: Talpaz

first: Lisa

last: Kujawski

first: Yang

first: Kerby

last: Shedden

first: Sajid

last: Shakhan

first: Cheng

last: Li

first: Harry

last: Erba


title: Frequent and Focal FGFR1 Amplification Associates With Therapeutically Tractable FGFR1 Dependency in Squamous-cell Lung Cancer.

status: Public on Dec 16 2010

city: Cologne

first: martin

last: sos

address: Gleuelerstr. 50

country: Germany

institute: Max-Planck Institute for neurological research

summary:
We analyzed 155 squamous- cell lung cancer and 77 adenocarcinoma of the lung samples using 6.0 SNP-arrays
all normal tissues that were used to infer copy number are provided

overall_design: DNA was extracted from fresh frozen tissues and copy number data was generated for all samples

first: Roman

middle: K

last: Thomas


title: Identification of SNP candidates associated with chemo-responsiveness in colorectal cancer patients

status: Public on Mar 25 2011

city: Daejon

first: Seon-Young

last: Kim

address: 52 Eoeun-dong, Yuseong-gu

department: Genome Research Center

country: South Korea

institute: Korea Research Institute of Bioscience and Biotechnology

summary:
Response rates of 118 colorectal cancer patients to regiments were evaluated by histoculture drug response assay. Affymetrix SNP 6.0 chips were used to determine genotypes of the same colorectal cancer patients. SNPs associated with chemosensitivity to treatment regiments were identified by genome-wide association study.
AV: avastin (Bevacizumab), ER: Erbitux (Cetuximab), FXA: bevacizumab + FOLFOX, FXE: Cetuximab + FOLFOX , FRA: Bevacizumab + FOLFIRI, FRE: Cetuximab + FOLFIRI; Numbers (0-100) represent responsiveness to the given drug regimens; the larger, the better responsive to given regimens

overall_design: SNP association with drug responsiveness

first: J

first: Y

middle: J

last: Jeon

first: H

middle: S

last: Ju

first: T

middle: W

last: Kang

first: S

middle: Y


title: Affymetrix SNP 6.0 array data for single cell multiple displacement amplification

city: Whan

first: Yan

last: Shea (Xie)

state: Hubei

address: Donghu Road 169#

country: China

institute: Wuhan University Zhongnan Hospital

summary: Generating sufficient DNA for high-throughput genetic analysis has always been a challenge for clinical settings where the amount of source DNA is limited. Multiple displacement amplification (MDA) has been proposed as a promising candidate for such situations. Previous work with lower-resolution arrays confirmed the utility of single-cell MDA products for large-size (~30 Mb) genome variation screening. We tested the performance of single-cell MDA products on the SNP 6.0 arrays to examine the performance of single-cell MDA in SNP genotyping, copy number polymorphism, de novo copy number variation (CNV) and loss of heterozygosity (LOH) analysis. Our data show that for SNP genotyping, single-cell MDA did not obtain complete genome coverage or high sequence fidelity. For CNV calling, single-cell MDA introduced stochastic amplification artifacts in log2 ratio profiles, reducing the robustness of CNV calling; however, by adjusting smooth window size, it is still possible to analyze large chromosomal aberrations, and homozygous deletions as small as 500 kb can still be identified from the noisy log2 ratio profiles. Our results also suggest that even with a modified protocol (reduction of reaction volume, addition of a molecular crowding reagent, minimization of reaction time), single-cell MDA presented little improvement over the unmodified protocol, but by increasing the number of cells as template to 5–10 cells, SNP 6.0 array results comparable to those of 10 ng genomic DNA MDA could be obtained. Algorithms like PICNIC improved the CNV calling, suggesting that better algorithms can better utilize single-cell MDA array results.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cell line samples, and multiple displacement samples.
Genotyping, Copy number and LOH analysis of Affymetrix SNP 6.0 arrays was performed for 3 samples of unamplified cell line genomic DNA, 2 samples of DNA obtained by multiple displacement amplification from 10ng genomic DNA, 3 single-cell multiple displacement amplification (MDA) products, single cell modified MDA amplification product, 5-cell modified MDA amplification product, 10-cell  modified MDA amplification product.

last: Xie

first: Xin

last: Zhou


title: Identification of candidate predisposing copy number variants in familial and early-onset colorectal cancer patients

status: Public on Nov 01 2010

city: Nijmegen

first: Roland

middle: P.

last: Kuiper

address: Geert Grooteplein 10

department: Human Genetics

country: Netherlands

institute: Radboud University Nijmegen Medical Centre

summary:
In the majority of colorectal cancers (CRC) under clinical suspicion for a hereditary cause, the disease-causing genetic factors are still to be discovered. In order to identify such genetic factors we stringently selected a discovery cohort of 41 CRC index patients with microsatellite-stable tumors. All patients were below 40 years of age at diagnosis and/or exhibited an overt family history. We employed genome-wide copy number profiling using high-resolution SNP-based array CGH on germline DNA, which resulted in the identification of novel copy number variants (CNVs) in 6 patients (15%) encompassing, among others, the cadherin gene CDH18, the bone morphogenetic protein antagonist family gene GREM1, and the breakpoint cluster region gene BCR. In addition, two genomic deletions were encountered encompassing two microRNA genes, hsa-mir-491/KIAA1797 and hsa-mir-646/AK309218. None of these CNVs has previously been reported in relation to CRC predisposition in humans, nor were they encountered in large control cohorts (>1,600 unaffected individuals). Since several of these newly identified candidate genes may be functionally linked to CRC development, our results illustrate the potential of this approach for the identification of novel candidate genes involved in CRC predisposition.
Copy number detection was performed using CNAG2.0 software for 250k SNP arrays and using the Affymetrix Genotyping Console v2.1 software for SNP 6.0 arrays, Reference genomes are included in this data set.

overall_design: Germline genomic DNA from 41 patients with early-onset microsatellite stable colorectal cancer was hybridized on Affymetrix Nsp/6.0 SNP-based arrays according to manufacturer's procedures.

first: R

last: Venkatachalam

first: E

middle: T

last: Verwiel

last: Kamping

last: Hoenselaar

last: Görgens

last: Schackert

middle: H

last: van Krieken

first: M

last: Ligtenberg

first: N

last: Hoogerbrugge

first: A

last: Geurts van Kessel


title: Acquired Genomic Copy Number Aberrations and Survival in Adult Acute Myelogenous Leukemia

status: Public on Nov 30 2010

first: Sami

last: Malek

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

summary:
Purpose: Genomic aberrations are of dominant importance to the biology and clinical outcome of patients with acute myelogenous leukemia (AML), and conventional karyotyping-based risk classifications are routinely used in clinical decision making in AML. One of the known limitations of karyotyping is the low sensitivity of this method to detect genomic abnormalities in the sub-megabase (Mb) to ~5 Mb range, and it is currently unclear whether overcoming this limitation with array-based high-resolution karyotyping could be clinically relevant. Furthermore, given the heterogeneity of molecular mechanisms/aberrations that underlie the risks inherent in conventional karyotyping-based risk classifications, it is likely that further refinements in genomic risk prognostication can be achieved. Here, we have analyzed FACS-sorted AML blast-derived and paired buccal DNA from 114 previously untreated prospectively enrolled AML patients for acquired genomic copy number changes and LOH using Affymetrix SNP 6.0 arrays, and we have correlated genomic lesion load and specific chromosomal abnormalities with patient survival.

Conclusions: Using multivariate analyses, we found that having ≥2 genomic lesions detected through SNP 6.0 array profiling approximately doubles the risk of death when controlling for age and karyotype-based risk. Finally, we identified an independent negative prognostic impact of p53 mutations, 17p-LOH or both on survival in AML.

overall_design: Experimental design: We analyzed DNA from highly purified AML blasts and paired buccal cells from 114 patients using ultra-high density Affymetrix SNP 6.0 array-based genomic profiling. Patients 1 and 211 lack a correlate normal sample.

first: Brian

last: Parkin

first: Harry

last: Erba

first: Peter

last: Ouillette

first: Diane

last: Roulston

first: Anjali

last: Purkayastha

first: Judith

last: Karp

first: Moshe

last: Talpaz

first: Lisa

last: Kujawski

first: Sajid

last: Shakhan

first: Cheng

last: Li

first: Kerby

last: Shedden


title: Clinical relevance of SKP2 alterations in metastatic melanoma

status: Public on Oct 21 2010

city: New York

first: Iman

last: Osman

state: NY

address: 522 First Avenue, SML405

department: Urology

institute: New York University School of Medicine

type: Genome binding/occupancy profiling by SNP array

summary:
Melanoma cell lines were genotyped to evaluate copy number differences between nodular melanoma (NM) and superficial spreading melanoma (SSM). Cell lines were also evaluated for copy number alterations in the SKP2/p27 axis.
Affymetrix SNP arrays were performed according to manufacturer's instructions using DNA extracted from 18 melanoma cell lines and 4 melanocyte controls.

overall_design:
Affymetrix SNP6.0 Array data for melanoma cell lines
Copy number analysis of Affymetrix SNP 6.0 arrays was performed on 18 melanoma cell lines including 2 primary superficial spreading melanoma, 2 primary nodular melanoma, 2 metastatic nodular melanoma, and 12 metastatic cell lines. Four melanocyte control lines were also evaluated including 2 immortalized melanocyte cell lines (Hermes 1 and 2B) and 2 normal melanocyte lines cultured from neonatal foreskin (HEM-N and HEM-LP) that were used to construct the baseline for copy number analysis.


title: Affymetrix SNP array data for EZH2 mediated gene copy number change in breast tumor initiating cells

status: Public on Sep 17 2010

city: Houston

first: Mien-chie

last: Hung

state: Texas

address: 1515 Holcomb Blvd

department: Molecular and Cellular Oncology

institute: M.D. Anderson Cancer Center

summary: EZH2 is shown to be involved in regulation of DNA damage repair which may contribute to development of breast tumor initiating cells. To identify genomic aberrations regulated by EZH2 expression, we performed genome wide copy number variation analysis in breast tumor initiating cells expressing EZH2 compared to the vector control. This finding suggests EZH2 contributes to oncogenic amplification in breast tumor initiating cells.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from primary breast tumor initiating cells infected with EZH2 or Vector control constructs
Copy number variation analysis of Affymetrix SNP 6.0 arrays was performed and compared between EZH2 and Vector control infected groups

first: C-J

last: Chang

first: M-C


title: Copy number data from GIST with KIT mutation

status: Public on Aug 27 2010

city: Bologna

first: Maria

middle: Abbondanza

last: Pantaleo

state: BO

address: via Massarenti 9

department: Institute of Hematology and Medical Oncology "L.A.Seragnoli"

country: Italy

institute: Policlinico S. Orsola-Malpighi, University of Bologna

summary:
In addition to KIT and PDGFRA mutations, sequential accumulation of other genetic events is involved in the development and progression of gastrointestinal stromal tumors (GISTs). Until recently, the significance of these other alterations has not been thoroughly investigated. The combination of gene expression profiling and high-resolution genomic copy number analysis offers a detailed molecular portrait of GISTs, providing an essential comprehensive knowledge necessary to guide the discovery of novel target genes involved in tumor development and progression.
Fresh tissue specimens from 25 patients with GIST were collected and high-resolution genomic copy number analyses were performed using Affymetrix SNP array 6.0.

overall_design: GIST tumor samples from mutated (KIT or PDGFRA) or Wild Type patients were labeled for hybridization on Affymetrix microarrays. Copy number analysis of Affymetrix SNP6.0 arrays was performed for 25 GIST samples, then compared to gene expression data.

first: Annalisa

last: Astolfi

first: Margherita

last: Nannini

middle: A

first: Monica

last: Di Battista

first: Michael

middle: C

last: Heinrich

first: Donatella

last: Santini

first: Fausto

last: Catena

first: Christopher

middle: L

last: Corless

first: Alessandra

last: Maleddu

first: Maristella

last: Saponara

first: Cristian

last: Lolli

first: Valerio

last: Di Scioscio

first: Serena

last: Formica

first: Guido

last: Biasco


title: Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma

status: Public on Oct 07 2010

city: Boston

middle: Richard

last: Green

state: MA

address: 44 Binney Street

department: Medical Oncology

institute: Dana-Farber Cancer Institute

summary: We integrate high-resolution copy number data with transcriptional profiles and identify the immunoregulatory genes, PD-L1 and PD-L2, as key targets at the 9p24.1 amplification peak in HL and MLBCL cell lines.

overall_design: DNA copy number alterations were defined in DLBCL and HL cell lines, normalized to healthy donors, by GISTIC analysis of Affymetrix SNP 6.0 single nucleotide polymorphism microarray data. Using this analysis, we identified 9p24 amplification to be over-represented in HL cell lines compared to DLBCL cell lines.

middle: R

first: Stafano

last: Monti

first: Kunihiko

last: Takeyama

first: Margaret

last: Shipp


title: Prospective comparison of genome-wide aCGH platforms for the detection of CNVs in MR (GenomeWideSNP_6)

first: Tracy

last: Tucker

summary: Clinical laboratories are adopting array comparative genomic hybridization (AGH) as a standard clinical test. A number of whole genome AGH systems are available, but little is known about the comparative performance in a clinical context.  We prospectively studied 30 children with idiopathic MR and both unaffected parents of each child using Affymetrix 500K GeneChip SNP arrays, Agilent Human Genome 244K oligonucleotide arrays and NimbleGen 385K Whole-Genome oligonucleotide arrays. We determined whether CNVs called on these platforms were detected by Illumina Hap550 beadchips or SMRT 32K BAC whole genome tiling arrays and tested 15 of the 30 trios on Affymetrix 6.0 SNP array.  The Affymetrix 500K, Agilent and NimbleGen platforms identified 3061 autosomal and 117 X chromosome CNVs in 30 trios. 147 of these CNVs were de novo, but only 33 (22%) of the de novo CNVs were found on more than one platform. Performing genotype-phenotype correlations, we identified 7 pathogenic and 4 possibly pathogenic CNVs for MR. All 11 of these CNVs were detected by both the Agilent and NimbleGen arrays, 9 by the Affymetrix 500K and Illumina beadchips, and 5 by the SMRT BAC array. Two of the 4 pathogenic or possibly pathogenic CNVs present in the trios tested with the Affymetrix 6.0 array were identified.   Our findings demonstrate that different results are obtained with different AGH platforms and illustrate the trade-off that exists between sensitivity and specificity. The large number of apparently false positive CNV calls supports the need for validating clinically important findings with a different methodology.

overall_design: 15 trios were analysed consisting of child (proband) and both normal parents. We performed separate hybridizations for the mother, father, and child and then performed pair-wise comparisons of the normalized hybridization intensities for the child to the mother and of the child to the father in silico.

first: Alexandre

last: Montpetit

first: David

last: Chai

first: Susanna

last: Chan

first: Sébastien

last: Chénier

first: Bradley

middle: P

last: Coe

first: Allen

last: Delaney

first: Patrice

last: Eydoux

first: Wan

last: Lam

first: Sylvie

last: Langlois

first: Emmanuelle

last: Lemyre

first: Marco

last: Marra

first: Hong

last: Qian

first: Guy

last: Rouleau

last: Vincent

first: Jacques

last: Lmichaud

first: Jan

middle: M

last: Friedman


title: Large rare Deletions in Ashkenazi Jewish schizophrenia cases vs controls

status: Public on Aug 06 2010

city: Atlanta

first: Jennifer

middle: Gladys

last: Mulle

state: GA

address: 615 Michael Street, Room 375, Whitehead Bldg

department: Department of Human Genetics

institute: Emory Univeristy School of Medicine

summary: Schizophrenia is a severe psychiatric illness that affects ~1% of the population and has a strong genetic underpinning. Recently, genome wide analysis of copy number variation (CNV) has implicated rare and de novo events as important in schizophrenia.  Here we report a genome-wide analysis of 245 schizophrenia cases and 490 controls, all of Ashkenazi Jewish descent. Since many studies have found an excess burden of large, rare deletions in cases, we limited our analysis to deletions over 500 kb in size. We observed seven large, rare deletions in cases with 57% of these being de novo. We focused on one 836 kb de novo deletion at chromosome 3q29 that falls within a 1.3–1.6 Mb deletion previously identified in children with intellectual disability (ID) and autism, as increasing evidence suggests an overlap of specific rare CNVs between autism and schizophrenia. By combining our data with prior CNV studies of schizophrenia and analysis of the data of the Genetic Association Information Network (GAIN), we identified six 3q29 deletions among 7,545 schizophrenic subjects and one among 39,748 controls, resulting in a statistically significant association with schizophrenia (p = 0.02) and an odds ratio estimate of 17 (95% CI: 1.36–1198.4). Moreover, this 3q29 deletion region contains two linkage peaks from prior schizophrenia family studies, and the minimal deletion interval implicates 20 annotated genes, including PAK2 and DLG1, both paralogous to X-linked ID genes and now strong candidates for schizophrenia susceptibility.

overall_design: Copy Number alanysis was performed on 245 cases and 490 controls of Ashkenazi Jewish descent.  Samples were analyzed for deletions greater than 500 kb, with 20 or more snps in the interval.  Three algorithms were used for analysis, GADA, GLAD and BEAST.  The reference was created by using all samples processed here as the reference.

middle: G

first: Stephen

last: Warren


title: Population genetic structure of the Ashkenazi Jewish population

status: Public on Aug 16 2010

first: Steven

last: Bray

address: 615 Michael Street

institute: Emory University School of Medicine

summary: The Ashkenazi Jewish population has long been considered a genetic isolate and presumed to have the genetic signatures of founder effects and isolation. We genotyped a large cohort of Ashkenazi Jews and analyzed their genetic structure compared to other worldwide populations.

overall_design: We genotyped 471 normal control Ashkenazi Jewish individuals with the Affymetrix 6.0 array and analyzed their genetic structure relative to other Europe and worldwide populations.  We measured heterozygosity, linkage disequilibrium, identity-by-descent and used extended haplotype tests of positive selection.

first: Bray

last: Steven M.

first: Warren

last: Stephen T.


title: Homologous recombination between nonhomologous chromosomes – Recurrent chromosomal translocations mediated by interchromosomal NAHR

status: Public on Aug 17 2010

first: zhishuo

last: ou

state: TX

address: One Baylor Plaza

department: Molecular and Human Genetics

institute: Baylor College of medicine

summary: Four unrelated families with the same unbalanced translocation der(4)t(4;11)(p16.2;p15.4) were identified.  Both of the breakpoint regions in 4p16.2 and 11p15.4 were narrowed to large ~359-kb and ~215-kb low-copy repeat (LCR) clusters, respectively, by aCGH and SNP array analyses. DNA sequencing enabled mapping the breakpoints of one translocation to 24-bp within interchromosomal paralogous LCRs of ~130-kb in length and 94.7% DNA sequence identity located in olfactory receptor gene clusters, indicating nonallelic homologous recombination (NAHR) as the mechanism for translocation. To investigate the potential involvement of interchromosomal LCRs in recurrent chromosomal translocation formation, we performed computational genome-wide analyses and identified 5292 interchromosomal LCR substrate pairs, > 5-kb in size and sharing > 94% sequence identity that can potentially mediate chromosomal translocations. Additional proof for interchromosomal NAHR mediated translocation formation was provided by sequencing the breakpoints of another recurrent translocation, der(8)t(8;12)(p23.1;p13.31). The NAHR sites were mapped within 55-bp in ~7.8-kb paralogous subunits of 95.3% sequence identity located in the ~579-kb (chr8) and ~287-kb (chr12) LCR clusters. We demonstrate that NAHR mediates recurrent constitutional translocations throughout the human genome and provide a computationally determined genome-wide “recurrent translocation map”.

overall_design:
Affymetrix Genome-Wide SNP Array 6.0 arrays (Affymetrix, Santa Clara, California) were employed to define the breakpoints on chromosomes 4, 8, 11, and 12. Analysis was performed according to the Genome-Wide Human SNP Nsp/Sty Assay Kit 5.0/6.0 protocol provided by the supplier. The arrays were scanned using a GeneChip® Scanner 3000 7G (Affymetrix, Inc.) and results were analyzed using Genotyping Console version 2.1 software.

patient 1: Version 5 BAC array contained 853 BAC/PAC clones designed to cover genomic regions of 75 known genomic disorders, all 41 subtelomeric regions, and 43 pericentromeric regions. For each patient sample, two experiments were performed with reversal of the dye labels for the control and test samples.
patient 2: Version 5.1 BAC array contained 853 BAC/PAC clones designed to cover genomic regions of 75 known genomic disorders, all 41 subtelomeric regions, and 43 pericentromeric regions. For each patient sample, two experiments were performed with reversal of the dye labels for the control and test samples.
patient 3: The BAC emulated Version 6.1 OLIGO array was comprised of approximately 42,460 oligonucleotides representing 1400 BAC clones, covering ~150 genomic disorders, all 41 subtelomeric regions up to 12 Mb and 43 pericentromeric regions with backbone coverage of every chromosome at the 650-band level of cytogenetic resolution (http://www.bcm.edu/geneticlabs/cma/tables.html). The 42.46K oligonucleotides (oligos) were selected from initial testing of 105,000 oligos derived from the Agilent eArray library with strict selection criteria and removal of repetitive sequences to ensure optimal performance with greater dynamic range. This targeted 42.46 K OLIGO array (V6 OLIGO) corresponds to genomic regions covered by the V6 BAC arrays and was manufactured in a 4 x 44K format with an average of 28-30 oligos per region previously covered by a single BAC clone.
patient 5: The BAC emulated Version 6.3 OLIGO array was comprised of approximately 43,580 oligonucleotides representing 1400 BAC clones, covering ~150 genomic disorders, all 41 subtelomeric regions up to 12 Mb and 43 pericentromeric regions with backbone coverage of every chromosome at the 650-band level of cytogenetic resolution (http://www.bcm.edu/geneticlabs/cma/tables.html). This targeted  OLIGO array  corresponds to genomic regions covered by the V6 BAC arrays and was manufactured in a 4 x 44K format with an average of 28-30 oligos per region previously covered by a single BAC clone.
patient 6: The BAC emulated Version 6.4 OLIGO array was comprised of approximately 43,700 oligonucleotides representing 1400 BAC clones, covering ~150 genomic disorders, all 41 subtelomeric regions up to 12 Mb and 43 pericentromeric regions with backbone coverage of every chromosome at the 650-band level of cytogenetic resolution (http://www.bcm.edu/geneticlabs/cma/tables.html). This targeted  OLIGO array  corresponds to genomic regions covered by the V6 BAC arrays and was manufactured in a 4 x 44K format with an average of 28-30 oligos per region previously covered by a single BAC clone.

Patient 4 was a known t(4;11) translocation patient form previous report and only ran on Affymetrix array.

first: Zhishuo

last: Ou

first: Paweł

last: Stankiewicz

first: Zhilian

last: Xia

first: Amy

last: Breman

first: Brian

last: Dawson

first: Joanna

last: Wiszniewska

first: Przemyslaw

last: Szafranski

first: M

last: Cooper

first: Mitchell

last: Rao

first: Lina

last: Shao

first: Sarah

last: South

first: Karlene

last: Coleman

last: Fernhoff

first: Marcel

middle: J

last: Deray

first: Sally

last: Rosengren

first: Elizabeth

last: Roeder

first: Victoria

middle: B

last: Enciso

first: A

last: Chinault

first: Ankita

last: Patel

first: Sung-Hae

last: Kang

first: Chad

last: Shaw

first: James

last: Lupski

first: Sau

last: Cheung


title: Affymetrix SNP6.0 microarray data - Myelodysplastic syndromes

status: Public on Jul 30 2010

city: London

first: Bartlomiej

middle: Przemyslaw

last: Przychodzen

address: Coldharbour Lane

department: Department of Haematology

country: United Kingdom

institute: King's College

summary: Mutations in the TET2 gene are frequent in myeloid disease, although their biological and prognostic significance remains unclear.  We analyzed 355 patients with myelodysplastic syndromes using ‘Next-Generation’ sequencing (NGS) for TET2 aberrations; 91 of whom were also subjected to SNP6 array karyotyping. Seventy-one TET2 mutations, with a relative mutation abundance (RMA) ≥10%, were identified in 39 of 320 (12%) MDS and 16 of 35 (46%) CMML patients (p<0.001). Interestingly, 4 patients had multiple mutations likely to exist as independent clones or on alternate alleles, suggestive of clonal evolution. ‘Deeper’ sequencing of 96 patient samples identified 4 additional mutations (RMA 3%-6.3%). Importantly, TET2 mutant clones were also found in T cells in addition to CD34+ and total bone-marrow cells (23.5%, 38.5% and 43% RMA respectively). Only 20% of the TET2-mutated patients showed loss of heterozygosity at the TET2 locus. There was no difference in the frequency of genome-wide aberrations, TET2 expression or the JAK2V617F 46/1 haplotype between TET2-mutated and non-mutated patients. There was no significant prognostic association between TET2 mutations and WHO subtypes, IPSS score, cytogenetic status, or transformation to AML. On multivariate analysis, age (>50yrs) was associated with a higher incidence of TET2 mutation (p=0.02).

overall_design: Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from bone marrow or peripheral blood samples. Copy number and acquired UPD analysis of Affymetrix SNP 6.0 arrays was performed for 91 cases with Myelodysplastic syndromes.

first: Azim

last: Mohamedali

first: Ghulam

last: Mufti


title: Affymetrix SNP array data for 31 Tibetan samples

status: Public on Jul 22 2010

city: Salt Lake City

first: T

last: Simonson

state: UT

address: 15 North 2030 East

institute: University of Utah

summary: This data was used to identify regions of the genome that have undergone positive selection in a high-altitude Tibetan population.

overall_design: Affymetrix SNP arrays were used to genotype DNA extracted from blood samples.  This data was used to perform genome-wide scans of positive selection in a native high-altitude Tibetan population.

first: Josef

last: Prchal

first: Lynn

last: Jorde

first: Rili

last: Ge


title: Affymetrix SNP 6.0 array data for myelodysplastic/myeloproliferative neoplasms

status: Public on Jun 30 2010

city: Salisbury

first: Andy

last: Chase

address: Salisbury District Hospital

institute: Wessex Regional Genetics Laboratory

summary: Abnormalities of chromosome 7q are common in myeloid malignancies but no specific target genes have been identified. Here we describe the finding of homozygous EZH2 mutations in 9 of 12 cases with 7q acquired uniparental disomy. Screening of a total of 614 cases with myeloid disorders revealed 49 monoallelic or biallelic EZH2 mutations in 42 individuals, most commonly myelodysplastic/myeloproliferative neoplasms (27/219; 12%) and myelofibrosis (4/30; 13%). EZH2 encodes the catalytic subunit of the Polycomb repressive complex 2 (PRC2), the highly conserved histone H3 lysine 27 methyltransferase that influences stem cell renewal by epigenetic repression of genes involved in cell fate decisions. EZH2 has oncogenic activity and its overexpression has been causally linked to differentiation blocks in epithelial tumors. Unexpectedly, the mutations we identified resulted in premature chain termination or direct abrogation of histone methyltransferase activity, suggesting that EZH2 acts as a tumor suppressor for myeloid malignancies.

overall_design:
Affymetrix SNP 6.0 arrays were performed according to the manufacturer's directions on DNA extracted from bone marrow or peripheral blood samples.
Copy number and acquired UPD analysis of Affymetrix  SNP 6.0 arrays was performed for 148 atypical myeloproliferative neoplasms.

first: Andrew

first: Thomas

last: Ernst

first: Nicholas

last: Cross


title: Myelodysplastic/myeloproliferative neoplasms

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

overall_design: Refer to individual Series


title: Definitive SNP/CNV haplotype map of Asians determined using a collection of complete hydatidiform moles (Affymetrix)

status: Public on May 17 2010

city: Fukuoka

first: Kenshi

last: Hayashi

address: Maidashi 3-1-1, Higashi-ku

department: Medical Institute of Bioregulation

country: Japan

institute: Kyushu University

summary: Copy number variations (CNVs) are abundant, possibly variable among populations, and can confer various phenotypic variations such as risk to complex disease. We determined a genome-wide high resolution SNP/CNV haplotype structure of Asians, by analyzing a collection of complete hydatidiform moles (CHMs) of Japanese, using high-density DNA arrays. CHMs are tissues carrying duplicated haploid genomes that originated from single sperm, and have advantages as materials over conventional diploid cells in detecting CNVs by hybridization, because greater S/N ratios are expected, and overlapping CNV segments are independently detected without being bothered by possible heterozygous situations. Overall occupancy of CNV segments per haploid found here was at a level similar to previous reports. Approximately a half of our polymorphic CNV regions have not been described in the previous report for Asians, but the frequencies of most of these new CNV regions were low. The limited number of examined samples is likely to be the reason that they have escaped detection in the previous report. Many common CNV regions are resolvable to clusters of CNV segmets (that is, CNV events) on the basis of mutual overlap of the segments. The similarity of haplotype backgrounds surrounding different CNV events within the same CNV regions suggests that ancestral recurrences of CNV events were predominantly haplotype preferential.

overall_design:
SNP 6.0 array (Affymetrix) analyses were performed according to the manufacturer's directions on DNA extracted from 100 complete hydatidiform moles (CHMs) tissues collected throughout Japan.
Copy number analysis was performed for 100 CHM samples. All samples were also used as references for copy number inference.

first: Yoji

last: Kukita

first: Koji

last: Yahara

first: Koichiro

last: Higasa

first: Tomoko

last: Tahira

first: Kiyoko

last: Kato

first: Norio

last: Wake


title: Distinct genomic differences in prostate cancer between Western countries and China

status: Public on May 15 2010

first: Xueying

last: Mao

address: Charterhouse Square

institute: Queen Mary

summary: The reason why prostate cancer is significantly more common in Western than Asian men is unknown. Using a genome-wide approach to compare the genomic changes in prostate cancer tissues, we determined that those from Chinese patients lack key somatic genomic changes commonly found in Western patients, including the 21q22.2-22.3 deletion which causes the TMPRSS2:ERG fusion gene, and 10q deletion which leads to PTEN inactivation. The results were confirmed and their consequence on ERG expression was identified by study of a large series of Chinese and UK samples using tissue-microarrays. Subsequently, we identified significant AR genotype differences between UK and Chinese prostate cancer patients. The identification of specific somatic genomic differences in cancers from distinct populations may provide an opportunity to identify cancer-causing or protective factors.

overall_design: Copy number analysis of Affymetrix SNP 6.0 array  was performed for 5 UK and 39 Chinese prostate cancer. Except 6 Chinese samples, all other samples have case-matched normal controls. Unpaired Chinese tumor samples were analyzed against a baseline from 33 Chinese normal prostate samples.

first: Yongwei

last: Yu

first: Lara

middle: K

last: Boyd

first: Liyan

last: Xue

first: Guoping

last: Ren

first: Dongmei

last: Lin

first: Tracy

last: Chaplin

first: Sakunthala

last: Kudahetti

first: Elzbieta

last: Stankiewicz

first: Luis

last: Beltran

first: Manu

last: Gupta

first: R

last: Oliver

first: Nick

last: Lemoine

first: Dan

last: Berney

first: Bryan

middle: D

last: Young

first: Yong-Jie

last: Lu


title: Affymetrix SNP array data for Diffuse Intrinsic Pontine Glioma

status: Public on Jun 08 2010

city: Toronto

first: Pawel

last: Buczkowicz

state: Ontario

address: 686 Bay Street

department: Paediatric Laboratory Medicine

institute: Hospital for Sick Children

summary: Diffuse intrinsic pontine glioma (DIPG) is one of the most devastating of paediatric malignancies and one for which no effective therapy exists. A major contributor to the failure of therapeutic trials is the assumption that biologic properties of brainstem tumours in children are identical to cerebral high-grade gliomas of adults. A better understanding of the biology of DIPG itself is needed in order to develop agents targeted more specifically to these children’s disease. Here we address this lack of knowledge by performing the first high-resolution SNP-based DNA microarray analysis of a series of DIPGs. Eleven samples (nine post-mortem and two pre-treatment surgical samples), the largest series thus far examined, were hybridized to Affymetrix SNP arrays (250k or 6.0). The study was approved by the Research Ethics Board at our institution (Hospital for Sick Children, Toronto, Ontario, Canada). All Array findings were validated using quantitative-PCR, fluorescence in-situ hybridization, immunohistochemistry and/or microsatellite analysis. Analysis of DIPG copy number alterations showed recurrent changes distinct from those of paediatric supratentorial high-grade astrocytomas. 36% of DIPGs had gains in PDGFRA and all showed PDGF-R-α expression. Gains in PARP-1 were identified in 3 cases. Pathway analysis revealed genes with loss of heterozygosity were enriched for DNA repair pathways. Our data provides the first, comprehensive high-resolution genomic analysis of paediatric DIPG. Our findings of recurrent involvement of the PDGFR pathway as well as defects in DNA repair pathways coupled with gain of PARP-1 highlight two potential, biologically-based, therapeutic targets directed specifically at this devastating disease.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from snap frozen biopsy and autopsy brain tissue  from DIPG patients.
Copy number analysis of Affymetrix 250K and 6.0 SNP arrays was performed for 11 paediatric DIPG samples, 7 matched normal brain samples, and HapMap samples.

first: Maryam

last: Zarghooni

first: Ute

last: Bartels

first: Eric

last: Lee

first: Andrew

last: Morrison

first: Annie

last: Huang

last: Bouffet

first: Cynthia

last: Hawkins


title: Definitive SNP/CNV haplotype map of Asians determined using a collection of complete hydatidiform moles

first: Kenshi

last: Hayashi


title: Copy number analysis of spontaneously transformed hTERT-immortalized ovarian surface epithelial cells

status: Public on Nov 19 2010

first: Hagen

last: Kulbe

department: Centre for Cancer and Inflammation

institute: Institute of Cancer and the CR-UK Clinical Centre, Barts and The London School of Medicine and Dentistry

summary: We present evidence for cytogenetic changes in two transformed ovarian surface epithelium cell lines, TOSE1 and TOSE4. hTERT-immortalised ovarian surface epithelial cell line spontaneously transformed as measured by growth in soft agar. These cells were grown on plastic, and genomic DNA was extracted and analyzed for cytogenetic changes.

overall_design: The genotyping Affymetrix SNP6.0 arrays were used to define copy number changes in the TOSE1 and TOSE4 cell lines.

first: Kyra

last: Archibald


title: Acquired chromosome abnormalities in the lungs of patients with Pulmonary Arterial Hypertension

status: Public on May 01 2010

city: Aurora

first: Christopher

last: Coldren

state: CO

address: 12700 East 17th Place

department: Medicine

institute: University of Colorado School of Medicine

summary: Vascular remodeling in pulmonary arterial hypertension (PAH) involves proliferation and migration of endothelial and smooth muscle cells, leading to obliterative vascular lesions. Previous studies have indicated that the endothelial cell proliferation is quasi-neoplastic, with evidence of monoclonality and instability of short DNA microsatellite sequences. To assess whether there is larger scale genomic instability, we performed genome-wide microarray copy number analysis on pulmonary artery endothelial (PAEC) and smooth muscle cells isolated from the lungs of PAH patients. Mosaic chromosomal abnormalities were detected in five of nine PAEC cultures from PAH lungs and zero of four controls. Fluorescent in situ hybridization analysis confirmed the presence of these abnormalities in vivo in two of three cases. One patient harbored a germline mutation of BMPR2, the primary genetic cause of PAH, and a somatic loss of chromosome-13, which constitutes a second hit in the same pathway by deleting Smad-8. In two female cases with mosaic loss of the X-chromosome, methylation analysis showed that the active X was deleted. Remarkably, one also showed completely skewed X-inactivation in the non-deleted cells, suggesting the PAEC population was clonal prior to the acquisition of the chromosome abnormality. Our data indicate a high frequency of genetically abnormal sub-clones within the lung vessels of patients with PAH and provide the first definitive evidence of a second genetic hit in a patient with a germline BMPR2 mutation. We propose that these chromosome abnormalities may confer a growth advantage and thus contribute to the progression of PAH.

overall_design:
Cross-sectional study of genomic copy number in cells cultured from the lungs of PAH patients.
This study used three Affy SNP chip types: 250kNSP, 250kSTY, and 6.0

first: Micheala

last: Aldred

first: Suzy

last: Comhair

first: Marileila

last: Varella-Garcia

first: Kewal

last: Asosingh

first: Weiling

last: Xu

first: George

last: Noon

first: Patricia

last: Thistlethwaite

first: Rubin

last: Tuder

first: Serpil

last: Erzurum

first: Mark

middle: W

last: Geraci


title: Affymetrix SNP6.0 array for comparison of lung tumor and adjacent normal to high-throughput sequencing data

status: Public on May 27 2010

city: South San Francisco

first: Peter

last: Haverty

state: CA

address: 1 DNA Way

department: Bioinformatics

institute: Genentech, Inc.

summary:
One lung tumor and its adjacent normal were profiled for copy-number alterations with the high-resolution Affymetrix SNP6.0 Array.

The SRA ID for the high throughput sequencing project will accompany our study is SRP002045.

overall_design: One lung tumor sample and an adjacent normal sample were assayed on the Affymetrix SNP6.0 array.

first: William

last: Lee

first: Jiang

last: Zhaoshi

first: Jinfeng

last: Liu

first: Yinghui

last: Guan

first: Jeremy

last: Stinson

first: Peng

last: Yue

first: Yan

last: Zhang

first: Krishna

last: Pant

first: Deepali

last: Bhatt

first: Connie

last: Ha

first: Stephanie

last: Johnson

first: Michael

middle: I

last: Kennemer

first: Sankar

last: Mohan

first: Igor

last: Nazarenko

first: Colin

last: Watanabe

first: Andrew

last: Sparks

first: David

middle: S

last: Shames

first: Robert

last: Gentleman

first: Howard

last: Stern

first: Ajay

last: Pandita

first: Dennis

last: Ballinger

first: Radoje

last: Drmanac

first: Zora

last: Modrusan

first: Somasekar

last: Seshagiri

first: Zemin


title: Genome-wide copy number variation in TP53 mutation negative ovarian tumours

status: Public on Mar 04 2010

city: East Melbourne

first: Dariush

last: Etemadmoghadam

address: St Andrew's Place

country: Australia

institute: Peter MacCallum Cancer Centre

summary: Genome-wide copy number variation was measured in TP53 mutation negative ovarian tumours. Analysis described in "Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary" (Ahmed et al., 2010)

overall_design: 7 needle-dissected or whole tumours (>80% tumour content) were analysed by Affymetrix SNP 6.0 Microarrays

first: Ahmed

middle: A

last: Ahmed

first: Jillian

last: Temple

last: Lynch

first: Mohamed

last: Riad

first: Raghwa

last: Sharma

last: Stewart

first: Sian

last: Fereday

first: Carlos

last: Caldas

first: Anna

last: DeFazio

last: Bowtell

first: James

last: Brenton


title: Affymetrix SNP array data for melanoma short-term cultures and cell lines

status: Public on Feb 01 2010

city: Cambridge

first: Michael

last: Berger

address: 7 Cambridge Center

department: Cancer Program

institute: The Broad Instititute

summary:
SNP arrays were used to derive copy number estimates and identify amplifications and deletions in melanomas
These copy number breakpoints were compared to gene fusions identified by second generation sequencing of cDNA

overall_design:
Affymetrix SNP 6.0 array hybridizations were performed for 3 melanomas and 15 normal diploid samples (in a batch of 96 total samples encompassing multiple studies).

Further normalization performed to convert signal intensities (see Sample data tables) into copy number log2 ratios for each probeset (see supplementary file at the foot of this record) using the 5 most similar HapMap normals, as described by the Cancer Genome Atlast Research Network, Nature (2008), 455:1061-1068.

middle: F

first: Levi

last: Garraway


title: Affymetrix SNP 6.0 array data for human embryonic stem cell lines

status: Public on Mar 01 2010

city: Turku

first: Elisa

middle: Maarit

last: Närvä

address: Tykistönkatu 6

department: Turku Centre for Biotechnology

country: Finland

institute: University of Turku

summary:
Pluripotent human embryonic stem cells are studied for potential applications in regenerative cell replacement therapies because of their untransformed nature and unique capacity to self-renew and differentiate. However it is known that adaptation of hESCs occurs on prolonged culture and may be associated with the acquisition of chromosome abnormalities.
We report a high resolution DNA SNP 6.0 array analysis showing copy number variation in 17 different hESC lines maintained in different laboratories. Several of the changes were culture induced and changed the expression levels of affected genes. Loss of heterozygosity (LOH) of chromosome 16q was detected in one line, in addition to several smaller LOH regions. Importantly, hESCs were found to contain several CNVs less than 3 Mb in size which is below the detection limit of conventional karyotyping.

overall_design: Copy number analysis of Affymetrix SNP 6.0 arrays was performed for 29 hESC samples of various passages and laboratory origin. 40 reference HapMap samples from Affymetrix were hybridized at the same time to built a reference genome used in the analysis.

first: Reija

last: Autio

first: Nelly

last: Rahkonen

first: Lingjia

last: Kong

first: Neil

last: Harrison

first: Danny

last: Kitsberg

first: Lodovica

last: Borghese

first: Joseph

last: Itskovitz-Eldor

first: Omid

last: Rasool

first: Petr

last: Dvorak

first: Outi

last: Hovatta

first: Timo

last: Otonkoski

last: Tuuri

first: Wei

last: Cui

first: Oliver

last: Brüstle

first: Duncan

last: Baker

first: Edna

last: Maltby

first: Harry

last: Moore

first: Nissim

last: Benvenisty

first: Peter

last: Andrews

first: Olli

last: Yli-Harja

first: Riitta

last: Lahesmaa


first: Elisa

last: Närvä

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

summary:
High resolution genome wide DNA analysis on a large panel of Human Embryonic stem cell lines reveals loss of heterozygosity and copy number variation changes associated with culture and affecting gene expression

This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series.

first: Reija

last: Autio


title: Affymetrix U133A array data for 111 pediatric acute myeloid leukemia (AML) samples at diagnosis

status: Public on Jan 04 2010

city: Memphis

first: Jeffery

last: Klco

state: TN

address: 262 Danny Thomas Place

department: Pathology

institute: St Jude Children's Research Hospital

summary:
Genome-wide profiling of Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH), gene expression and resequencing of pediatric AML

This study characterizes CNA and LOH, gene expression and gene sequence mutations in a representative cross-section through subtypes of pediatric AML.

Keywords: Affymetrix arrays were performed according to the maufacturers directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. Samples with less than 80% blasts were flow sorted prior to DNA extraction

overall_design: 111 pediatric AML samples were studied using the Affymetrix U133A array.

first: Ina

last: Radtke

first: James

last: Downing


title: Enhanced Monocyte Response & Decreased Central Memory T Cells in Children with Invasive Staphylococcus aureus Infections

status: Public on May 30 2009

city: Dallas

first: Damien

last: Chaussabel

address: 3434 Live Oak

institute: Baylor Institute for Immunology Research

summary: Staphylococcus aureus has emerged as a significant pathogen causing severe, invasive disease in otherwise healthy people.  Despite considerable advances in understanding the epidemiology, resistance mechanisms, and virulence factors produced by the bacteria, there is limited knowledge of the in vivo host immune response to acute, invasive S. aureus infections.  Herein, we report that peripheral blood mononuclear cells from patients with severe S. aureus infections demonstrate a distinctive and robust gene expression profile which is validated in a distinct group of patients and on a different microarray platform.  Application of a systems-wide modular analysis framework reveals significant over-expression of  innate immunity genes and under-expression of genes related to adaptive immunity.  Simultaneous flow cytometry analyses demonstrated marked alterations in immune cell numbers, with decreased central memory CD4 and CD8 T cells and increased number of monocytes.  CD14+ monocyte numbers significantly correlated with the gene expression levels of genes related to the innate immune response.  These results demonstrate the value of applying a systems biology approach that reveals the significant alterations in the components of  circulating blood lymphocytes and monocytes in invasive S. aureus infections.

overall_design: Blood samples were collected from patients with S. aureus infections and healthy controls. 108 Affymetrix and 18 Illumina arrays.


title: SNP/CNV analysis in a breast cancer metastasis model

status: Public on Oct 02 2009

first: Ann

last: Chambers

address: 790 Commissioner's Road E

department: Victoria research labs

institute: London Regional Cancer program

summary: The Affymetrix SNP/CNV (SNP 6.0) platform was used to analyze a cell line model of lymph node metastasis comprised of a poorly metastatic MDA-MB-468GFP human breast adenocarcinoma cell line and its highly metastatic variant (468LN).

overall_design: DNA derived from 2 biological replicates of a highly metastatic (via lymph nodes) breast cancer cell line (468GFP-LN) was compared to 2 biological replicates of DNA prepared from the parental cell line, 468GFP.

first: David

last: Rodenhiser

first: Joseph

first: Wendy

last: Kennette

first: Jenn

last: Pilon

first: Alexandr

last: Hodgson

first: Alan

last: Tuck


title: Acquired mutations in TET2 are common in myelodysplastic syndromes

status: Public on May 28 2009

city: Nijmegen

first: Roland

middle: P.

last: Kuiper

address: Geert Grooteplein 10

department: Human Genetics

institute: Radboud University Nijmegen Medical Centre

summary: Myelodysplastic syndromes (MDS) represent a heterogeneous group of neoplastic hematopoietic disorders. Several recurrent chromosomal aberrations have been associated with MDS, but the genes affected have remained largely unknown. To identify relevant genetic lesions involved in the pathogenesis of MDS, we performed SNP-array-based genomic profiling and genomic sequencing in 102 patients. We identified acquired deletions, missense and nonsense mutations in a new gene, TET2, in 26% of MDS patients. Using allele-specific assays, TET2 mutations were shown to be present in the majority of the myeloid cells (56-100%, median 96%). In addition, the mutations were encountered in various lineages of differentiation including CD34+ progenitor cells, suggesting that TET2 mutations occur early during disease evolution. In healthy tissues TET2 expression was shown to be elevated in hematopoietic cells with highest expression in granulocytes, in line with a function in myelopoiesis. We conclude that TET2 is the most frequently mutated gene in MDS known so far.

overall_design: Genomic DNA from 102 bone marrow samples and 8 isolated T-cell fractions from MDS patients was hybridized on Affymetrix SNP arrays according to manufacturer's procedures. From one patient, T-cell fraction, mononuclear MDS fraction, and an AML diagnosis sample was hybridized on Affymetrix SNP 6.0 arrays.

first: S

last: Langemeijer

first: R

first: M

last: Berends

last: Knops

last: Aslanyan

last: Massop

first: E

last: Stevens-Linders

first: P

last: van Hoogen

first: A

last: van Kessel

last: Raymakers

last: Kamping

first: G

middle: E

last: Verhoef

last: Verburgh

last: Hagemeijer

last: Vandenberghe

first: T

last: de Witte

first: B

last: van der Reijden

first: J

middle: H

last: Jansen


title: Analysis of pediatric acute myeloid leukemia (AML) samples at diagnosis

first: Jeffery

last: Klco

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


title: Role of the Bas1p transcription factor in the transcriptional response associated to AICAR and SAICAR accumulation

status: Public on May 15 2009

city: PARIS

first: sophie

last: lemoine

address: 46 rue d'Ulm

department: Biologie

country: France

institute: Ecole Normale Supérieure

summary:
We investigated the role of Bas1p in the transcriptional response due to AICAR and SAICAR accumulation. In this work, global transcription analyses were combined to measurements of intracellular nucleotides pools by HPLC.

Keywords: Comparative genomic transcription analysis on total RNA from cells accumulating AICAR and SAICAR in a bas1 deletion context.

overall_design: One biological sample in dye swap

first: Benoît

last: Pinson

first: Fanny

last: Coulpier

first: Sophie

last: Lemoine

first: Bertrand

last: Daignan-Fornier


title: TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma

status: Public on Mar 24 2009

city: Kiel

first: Inga

last: Vater

address: Arnold-Heller-Strasse 3, Haus 10

department: Institute of Human Genetics

institute: Univeesity hospital Schleswig-Holstein

summary: Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas. It is characterized by the presence of rare Hodgkin and Reed/Sternberg (HRS) cells embedded in an extensive inflammatory infiltrate. Constitutive activation of nuclear factor-kappaB (NF-kappaB) in HRS cells which transcriptionally regulates expression of multiple anti-apoptotic factors and pro-inflammatory cytokines plays a central role in the pathogenesis of cHL (1, 2). In non-stimulated condition, NF-kappaB proteins are rendered inactive by binding to their inhibitors (IkappaB s), which sequester them in the cytoplasm. Stimulation of multiple receptors activates the IkappaB kinase (IKK) complex that phosphorylates IkappaB at two specific serine residues, followed by its ubiquitination and proteasomal degradation, thereby releasing NF-kappaB proteins and allowing their nuclear translocation (3). Recently, two studies provided further insights into the molecular mechanisms of IKK activation upon TNF stimulation (4, 5). Activation of the IKK complex and subsequent NF-kappaB activation requires Lys63 polyubiquitination of RIP1, a kinase which is recruited to the receptor upon TNF stimulation. IKK-gamma (NEMO), the regulatory subunit of the IKK complex, specifically recognizes these Lys63-linked polyubiquitins attached to RIP1 and thereby activates IKK and NF-kappaB (4, 5). A20 is an ubiquitin-modifying enzyme that inhibits NF-kappaB activation in succession of tumor necrosis factor (TNF) receptor and Toll-like receptor induced signals (6-8). This enzyme removes Lys63 linked ubiquitin chains from RIP1 and adds Lys48 polyubiquitins to RIP1, thereby targeting this factor for proteasomal degradation, thus explaining the molecular mechanism of NF-kappaB inhibition by A20 (6). A20 likely inhibits NF-kappaB acitivity also by additional means, including interaction with TRAF1 and TRAF2 (9).

overall_design: SNP 6.0 array (Affymetrix) analyses were performed according to the manufacturer's directions on DNA extracted from three Hodgkin cell lines (L1236, HDLM-2, U-HO1), HapMap samples included in the Genotyping Console Software 3.0 were used as references.

first: Roland

last: Schmitz

first: Martin-Leo

last: Hansmann

first: Verena

last: Bohle

first: Jose

last: Martin-Subero

first: Sylvia

last: Hartmann

first: Gunhild

last: Mechtersheimer

first: Wolfram

last: Klapper

first: Maciej

last: Giefing

first: Stefan

last: Gesk

first: Jens

last: Stanelle

first: Reiner

last: Siebert

first: Ralf

last: Küppers


title: High-resolution mapping of copy-number alterations with massively parallel sequencing

status: Public on Nov 14 2008

city: Chapel Hill

first: Derek

last: Chiang

state: NC

address: UNC Lineberger Cancer Center, 450 West Drive, CB #7295

department: Department of Genetics

institute: University of North Carolina

summary:
In order to benchmark the reproducibility of Affymetrix Genome-Wide Human SNP Array 6.0 for detecting copy-number alterations, we performed replicate hybridizations of 3 tumor cell lines and 2 paired normal cell lines obtained from the American Type Culture Collection (ATCC).
We calculated copy numbers at each SNP probeset by a custom copy-number pipeline (PMID: 18772890).  For each cell line, copy number data from replicate arrays are supplied in the accompanying matrix files.  For each SNP probeset, we calculated the median copy number across replicate arrays.
We compared the copy-number alterations detected by Circular Binary Segmentation segmentation of these arrays with statistical analyses of short sequence reads obtained from the Illumina/Solexa 1G GenomeAnalyzer.  Shotgun sequencing results can be found in the NCBI Short Read Archive, accession number SRP000246

Keywords: disease state analysis

overall_design: 21 replicates of HCC1143 (breast ductal carcinoma), 21 replicates of HCC1143BL (matched normal), 13 replicates of HCC1954 (breast ductal carcinoma), 11 replicates of HCC1954BL (matched normal), 1 replicate of NCI-H2347 (lung adenocarcinoma), 1 replicate of NCI-H2347BL (matched normal)

middle: Y

first: Gad

last: Getz

first: David

last: Jaffe

first: Michael

last: O'Kelly

first: Xiaojun

last: Zhao

first: Scott

middle: L

last: Carter

first: Carsten

last: Russ

first: Chad

last: Nusbaum

first: Matthew

last: Meyerson

first: Eric

last: Lander


title: Expression data for diagnosis acute lymphoblastic leukemia samples

status: Public on Oct 02 2008

first: Jeffery

last: Klco

summary:
We studied a cohort of 221 high-risk pediatric B-progenitor ALL patients that excluded known high risk ALL subtypes (BCR-ABL1 and infant ALL), using Affymetrix single nucleotide polymorphism microarrays, gene expression profiling and candidate gene resequencing. A CNA poor outcome predictor was identified using a semi-supervised principal components approach, and tested in an independent validation cohort of 258 pediatric B-progenitor ALL cases. Over 50 regions of recurring somatically acquired CNA, with the most frequently targeted genes encoding regulators of B-lymphoid development (66.8% of cases; with PAX5 targeted in 31.7% and IKZF1 in 28.6%). A CNA classifier identified a very poor outcome subgroup in the high-risk cohort (P=4.2x10-5) and was strongly associated with the presence of deletions involving IKZF1, which encodes the early lymphoid transcription factor IKAROS. This classifier, and IKZF1 deletions, also predicted poor outcome and elevated minimal residual disease at the end of induction therapy in the validation cohort. The gene expression signature of the poor outcome group was characterized by reduced expression of B lineage specific genes, and was highly related to the expressing signature of BCR-ABL1 ALL, a known high-risk ALL subtype also characterized by a high frequency of IKZF1 deletion.Somatically acquired deletions involving IKZF1 identify a very poor outcome subgroup of pediatric ALL patients. Incorporation of molecular tests to identify IKZF1 deletion in diagnostic leukemic blasts should improve the ability to accurately risk stratify patients for appropriate therapy.
Affymetrix U133A arrays were performed according to the maufacturers directions on RNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. Samples with less than 80% blasts were flow sorted prior to RNA extraction

overall_design:
One hundred seventy five pediatric B-progenitor ALL samples were studied using Affymetrix U133A.
Affymetrix U133A arrays were performed according to the maufacturers directions on RNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. Samples with less than 80% blasts were flow sorted prior to RNA extraction.

first: Charles

middle: G

last: Mullighan

first: James

middle: R

last: Downing


title: Identification of Novel Oncogene Loci in Ovarian Cancer through Integrated Copy Number and Expression Analysis

status: Public on Apr 19 2010

city: Melbourne

first: Manasa

last: Ramakrishna

state: Victoria

address: St Andrew's Pl

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

summary: Use of expression data to analyse ovarian cancer often yields long lists of genes that do not agree across various studies. Copy number however is more stable and can reliable predict important regions of change. Using matched copy number and expressiion data helps accurately identify novel drivers of ovarian cancer.

overall_design:
72 tumours for copy number analysis with 57 matching blood normals. Out of these 72, 68 produced good quality RNA for expression arrays. These 68 array samples and have been run in 10 batches by the same user. Batch number is recorded under characteristics.

The SNP6_Normalised-Copy-number.csv file appended below contains the copy number ratios relative to matching normal samples or a pooled baseline. In this file, probes on Chromosome Y and the Mitochondrion (MT) have been removed and the probesets are organised first by Chromosome and then by start position. Annotations for this were mapped in Partek using the Affymetrix GenomewideSNP6, CN and SNP annotation files, release number 23.

first: Louise

last: Williams

first: Samantha

last: Boyle

first: Jennifer

last: Bearfoot

first: Anita

last: Sridhar

first: Kylie

last: Gorringe

first: Ian

last: Campbell

first: Terence

middle: P

last: Speed


title: Molecular characterization of very early relapsed childhood ALL

status: Public on Sep 27 2006

city: Berlin

first: Renate

last: Kirschner-Schwabe

address: Augustenburger Platz 1

department: Pediatric Oncology/Hematology

institute: Charité - Universitätsmedizin Berlin

summary:
Purpose: In childhood acute lymphoblastic leukemia (ALL), approximately 25% of patients suffer from relapse. In recurrent disease, despite intensified therapy, overall cure rates of 40% remain unsatisfactory and survival rates are particularly poor in certain subgroups. The probability of long-term survival after relapse is predicted from well-established prognostic factors, i. e. time and site of relapse, immunophenotype and minimal residual disease. However, the underlying biological determinants of these prognostic factors remain poorly understood.
Results: We show here that patients with very early relapse of ALL are characterized by a distinctive gene expression pattern. We identified a set of 83 genes differentially expressed in very early relapsed ALL compared to late relapsed disease. The vast majority of genes was up-regulated and many were late cell cycle genes with a function in mitosis. In addition, samples from patients with very early relapse showed a significant increase in the percentage of S and G/2M phase cells and this correlated well with the expression level of cell cycle genes.
Conclusions: Very early relapse of ALL is characterized by an increased proliferative capacity of leukemic blasts and up-regulated mitotic genes. The latter suggests that novel drugs, targeting late cell cycle proteins, might be beneficial for these patients that typically face a dismal prognosis.
Keywords: disease state analysis

overall_design: We performed gene expression profiling on 60 prospectively collected samples of children with first relapse of acute lymphoblastic leukemia enrolled on the relapse trial ALL-REZ BFM 2002 of the Berlin-Frankfurt-Muenster study group.

first: Claudio

last: Lottaz

first: Joern

last: Toedling

first: Peter

last: Thein

first: Leonid

last: Karawajew

first: Cornelia

last: Eckert

first: Arend

last: von Stackelberg

first: Ute

last: Ungethuem

first: Dennis

last: Kostka

first: Andreas

last: Kulozik

first: Wolf-Dieter

last: Ludwig

first: Guenter

last: Henze

first: Rainer

last: Spang

first: Christian

last: Hagemeier

first: Karl

last: Seeger


title: Gene expression in primary acute lymphoblastic leukemia (ALL) associated with methotrexate treatment response

status: Public on Mar 15 2008

first: William

last: Evans

address: 332 N Lauderdale St

institute: St.Jude Children's Research Hospital

summary:
Genome-wide assessment of gene expression in primary acute lymphoblastic leukemia cells was performed to identify genomic determinants of MTX’s antileukemic effects. Reduction of circulating leukemia cells after in vivo methotrexate treatment served as a measure MTX's antileukemic effects.
Keywords: gene expression associated with drug response

overall_design: Gene expression in diagnostic primary acute lymphoblastic leukemia cells from bone marrow of 161 pediatric patients

first: Michael

middle: J

last: Sorich

first: Nicolas

last: Pottier

first: Deqing

last: Pei

first: Wenjian

last: Yang

first: Leo

last: Kager

first: Gabriele

last: Stocco

first: Cheng

last: Cheng

first: John

middle: C

last: Panetta

first: Ching-Hon

last: Pui

first: Mary

middle: V

last: Relling

first: Meyling

last: Cheok


title: Mapping of copy-number alterations with massively parallel sequencing

first: Derek

last: Chiang

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

overall_design: Refer to individual Series


title: Effect of AICAR and SAICAR accumulation on global transcription

first: sophie

last: lemoine


title: Gene expression in PBMCs from children with diabetes

status: Public on Sep 12 2007

first: Ellen

last: Grishman

address: 5323 Harry Hines Blvd

institute: UTSW Medical Center

summary:
Objective: We hypothesized that type 1 diabetes (T1D) is accompanied by changes in gene expression in peripheral blood mononuclear cells (PBMCs) due to dysregulation of adaptive and innate immunity, counterregulatory responses to immune dysregulation, insulin deficiency and hyperglycemia. Research Design and Methods: Microarray analysis was performed on PBMCs from 43 patients with newly diagnosed T1D, 12 patients with newly diagnosed type 2 diabetes (T2D) and 24 healthy controls. One and four month follow-up samples were obtained from 20 of the T1D patients.
Results: Microarray analysis identified 282 genes differing in expression between newlydiagnosed T1D patients and controls at a false discovery rate of 0.05. Changes in expression of interleukin-1β (IL1B), early growth response gene 3 (EGR3), and prostaglandin-endoperoxide
synthase 2 (PTGS2) resolved within four months of insulin therapy and were also observed in T2D suggesting that they resulted from hyperglycemia. With use of a knowledge base, 81/282 genes could be placed within a network of interrelated genes with predicted functions including apoptosis and cell proliferation. IL1B and the MYC oncogene were the most highly-connected genes in the network. IL1B was highly overexpressed in both T1D and T2D, whereas MYC was dysregulated only in T1D.
Conclusion: T1D and T2D likely share a final common pathway for beta cell dysfunction that includes secretion of interleukin-1β and prostaglandins by immune effector cells, exacerbating existing beta cell dysfunction, and causing further hyperglycemia. The results identify several targets for disease-modifying therapy of diabetes and potential biomarkers for monitoring treatment efficacy.
Keywords: Diabetes, microarray analysis, peripheral blood mononuclear cells

overall_design:
We obtained blood samples from 24 healthy volunteers, 43 newly diagnosed T1D patients and 12 newly diagnosed T2D patients. All study participants were between the ages of 2 and 18 years.  We collected samples one and four months after diagnosis from the last 20 of the T1D patients. For each time point one sample did not pass quality control and was dropped from the analysis. Patients with T2D were distinguished from T1D on the basis of age, body habitus,
presence (11/12 patients) of acanthosis nigricans, family history of type 2 diabetes (11/12 patients), and absence of autoantibodies to insulin, IA-2, and GAD65. We allowed low titers of insulin antibodies in T2D patients (< 4 U/mL), which have been previously reported. All but two
of the T1D patients with positive anti-insulin antibodies were also positive for at least one additional autoantibody.

last: Kaizer

first: Casey

last: Glaser

first: Damien

last: Chaussabel

first: Jacques

last: Banchereau

first: Virginia

last: Pascual

first: Perrin

last: White


title: Abnormal Expression Changes in AML

status: Public on Nov 01 2007

city: Seattle

last: Stirewalt

state: WA

address: 1100 Fairview Ave N, D5-112

department: Clinical Research Division

institute: Fred Hutchinson Cancer Research Center

summary:
Acute myeloid leukemia (AML) is one of the most common and deadly forms of hematopoietic malignancies.  We hypothesized that microarray studies could identify previously unrecognized expression changes that only occur only in AML blasts. We were particularly interested in those genes with increased expression in AML, believing that these genes may be potential therapeutic targets.
Keywords: AML vs Normal hematopoietic cells

overall_design: We compared gene expression profiles between normal hematopoietic cells from 38 healthy donors and leukemic blasts from 26 AML patients.  Normal hematopoietic samples included CD34+ selected cells (N = 18), unselected bone marrows (N = 10), and unselected peripheral bloods (N = 10).

first: Soheil

last: Meshinchi

first: Kenneth

last: Kopecky

first: Wenhong

last: Fan

first: Era

last: Pogosova-Agadjanyan

first: Julia

last: Engel

first: Michelle

last: Cronk

first: Kathleen

last: Shannon Dorcy

first: Amy

last: McQuary

first: David

last: Hockenbery

first: Brent

last: Wood

first: Shelly

last: Heimfeld

first: Jerald

last: Radich


title: Gene expression profiling of atypical T-ALL

first: Charles

last: Mullighan

summary:
Despite improved therapy, approximately one-fifth of children with acute T-lymphoblastic leukemia (T-ALL) succumb to the disease, suggesting unrecognized biologic heterogeneity that may contribute to drug resistance. We studied leukemic cells, collected at diagnosis, to identify features that could define this high-risk subgroup. A total of 139 patients with T-ALL were treated consecutively from 1992 to 2006 at this institution.  Their leukemic cells were examined with multiparameter flow cytometry, single nucleotide polymorphism arrays and other methods of genomic analysis.  Survival rates and probabilities of  treatment failure were calculated for subgroups considered to have biologically distinct forms of T-ALL.
The lymphoblasts of 17 patients (12.2%) had immunophenotypes that clearly differed from those of the remaining patients.  Most striking features were the low or absent expression of common T-lineage markers (CD5, CD1a and CD8), and expression of myeloid and stem cell markers, suggesting stem-cell like properties. These atypical blasts also showed a distinct gene expression profile and increased genomic instability overall. Patients with this form of T-ALL had a very low probability of surviving for 10 years after diagnosis:  19% ± 12% (mean ± SE) versus 84% ± 6% for all other patients ( P<0.001).  The cumulative incidence of remission failure / hematologic relapse was 72% ± 16% versus 10% ± 3% (P < 0.001). A subset of children with T-ALL have atypical blast cell immunophenotypes that predict a dire outcome with use of standard intensive chemotherapy.  Alternative treatment strategies are need for patients with this sybtype of leukemia.
Keywords: Analysis of gene expression profiles of typical versus atypical T-ALL

overall_design: 55 Diagnostic T-ALL samples were analyzed

first: Dario

last: Campana


status: Public on Apr 15 2004

city: Houston

first: Roel

last: Verhaak

address: 1400 Pressler St

department: Bioinformatics and Comp Bio

institute: MD Anderson Cancer Center

summary:
Expression profiles of acute myeloid leukemia patient samples.

Blasts and mononuclear cells were purified from bone marrow or peripheral blood aspirates of acute myeloid patients. Samples contained 80-100 percent blast cells. Total RNA was extracted by lyses with guanidium isothiocyanate followed by cesium chloride gradient purification
Keywords: other

first: Peter

middle: JM

last: Valk

middle: GW

first: Antoinette

last: Beijen

first: Claudia

middle: AJ

last: Erpelinck

first: Sahar

last: Barjesteh van Waalwijk van Doorn-Khosrovani

first: Judith

middle: M

last: Boer

first: Berna

last: Beverloo

first: Michael

last: Moorhouse

last: Van der Spek

first: Bob

last: Lowenberg

first: Ruud

last: Delwel