title: Quantification of Normal Cell Fraction and Copy Number Neutral LOH in Clinical Lung Cancer Samples Using SNP Array Data

status: Public on Aug 11 2009

first: Anders

last: Isaksson

summary: Technologies based on DNA microarrays have the potential to provide detailed information on genomic aberrations in tumor cells. In practice a major obstacle for quantitative detection of aberrations is the heterogeneity of clinical tumor tissue. Tumor tissue consists of a mixture of tumor cells and normal cells, including inflammatory and stromal cells, which may lead to a failure to detect aberrations in the tumor cells. Principal finding: Using SNP array data from 43 non-small cell lung cancer samples we have developed a bioinformatic algorithm that accurately models the fractions of normal and tumor cells in clinical tumor samples.

overall_design: The proportion of normal cells and SNP array data can be used to detect and quantify copy number neutral loss-of-heterozygosity (CNNLOH) in the tumor cells both in crude tumor tissue and in samples enriched for tumor cells by laser capture microdissection. Conclusion: Genome-wide quantitative analysis of CNNLOH using the CNNLOH Quantifier method can help to identify recurrent aberrations contributing to tumor development in clinical tumor samples. In addition, SNP-array based analysis of CNNLOH may become important for detection of aberrations that can be used for diagnostic and prognostic purposes, as well as to predict response to therapy.


title: Chromosomal duplication in the grandifolia-D mutants of Arabidopsis thaliana

status: Public on Jun 02 2009

city: Gent

first: Nathalie

last: Gonzalez

address: Technologiepark 927

department: Plant System Biology

country: Belgium

institute: VIB

type: Genome variation profiling by genome tiling array

summary:
The number of cells in an organ is a major factor for the determination of organ size. However, genetic basis of cell number determination is not well understood. Three grandifolia-D (gra-D) mutants of Arabidopsis thaliana developed huge leaves containing two- to three-fold increased number of cells of the wild type. Tiling array and microarray analysis of gra-D mutants suggested that genes found in a lower part of chromosome 4 were upregulated, suggesting the occurrence of segmental chromosomal duplications in the gra-D mutants. These region contain positive regulators of cell proliferation such as  AINTEGUMENTA (ANT) and cyclin genes such as CYCD3;1.

This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: IKZF1 deletions predict relapse in uniformly treated pediatric precursor B-ALL

status: Public on Mar 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

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

summary:
Relapse is the most common cause of treatment failure in pediatric acute lymphoblastic leukemia (ALL) and is often difficult to predict. To explore the prognostic impact of recurrent DNA copy number abnormalities on relapse, we performed high-resolution genomic profiling of 34 paired diagnosis-relapse ALL samples. Recurrent lesions detected at diagnosis, including PAX5, CDKN2A, and EBF1, were frequently absent at relapse, indicating that they represent secondary events that may be absent in the relapse-prone therapy-resistant progenitor cell. In contrast, deletions and nonsense mutations in IKZF1 (IKAROS), were highly enriched and consistently preserved at the time of relapse. A targeted copy number screen in an unselected cohort of 131 precursor B-ALL cases, enrolled in the dexamethasone-based Dutch Childhood Oncology Group treatment protocol ALL9, revealed that IKZF1 deletions are significantly associated with poor relapse-free and overall survival rates. Separate analysis of ALL9-treatment subgroups revealed that non-high-risk patients with IKZF1 deletions exhibited a ~12-fold higher relative relapse rate than those without IKZF1 deletions. Consequently, IKZF1 deletion status allowed the prospective identification of 53% of the relapse-prone non-high-risk-classified patients within this subgroup and, therefore, serves as one of the strongest predictors of relapse at the time of diagnosis with high potential for future risk stratification.
Affymetrix NspI 250k array data of 34 paired diagnosis and relapse samples of pediatric ALL. From 13 patients a complete remission sample was available. Four cases had 2 relapses.

overall_design: Genomic DNA from 86 bone marrow or periphearal blood was hybridized on Affymetrix NspI SNP-based arrays according to manufacturer's procedures

middle: P

first: Esmé

last: Waanders

first: Vincent

middle: H

last: van der Velden

first: Simon

middle: V

last: van Reijmersdal

first: Ramprasath

last: Venkatachalam

first: Blanca

last: Scheijen

first: Edwin

last: Sonneveld

first: Jacques

middle: M

last: van Dongen

first: Anjo

last: Veerman

first: Frank

middle: N

last: van Leeuwen

first: Ad

middle: G

last: van Kessel

first: Peter

last: Hoogerbrugge


title: Analysis of genomic instability in esophageal squamous cell carcinoma (ESCC)

status: Public on Jun 01 2009

city: Rockville

first: Robert

middle: J

last: Clifford

state: MD

address: 2115 E Jefferson

department: CCR

country: USA

institute: NCI

summary:
To characterize genomic instability in esophageal squamous cell carcinoma, we examined loss of heterozygosity,
copy number loss, and copy number gain in ESCC patients from a high-risk region of China.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from microdissected esophageal squamous cell carcinoma samples or peripheral blood samples.
Tumor DNA samples were normalized individually to the set of 102 peripheral blood samples.  Copy number variations and loss of heterozygosity were determined by a paired analysis of tumor and blood DNA from the same individual.

first: Maxwell

last: Lee

first: Phillip

middle: R

last: Taylor


title: miRNA profiling of FACS sorted human leukocyte cell types

status: Public on Nov 26 2009

city: Leuven

first: Rekin's

last: Janky

address: Herestraat 49 Box 816

department: Nucleomics Core

summary: Affymetrix miRNA arrays were used to generate miRNA profiles of peripheral blood leukocytes and FACS sorted neutrophils, monocytes, B-cells, T-cells, CD4+ T-cells, and CD8+ T-cells, being the major leukocyte cell types in human. The study allowed for the determination of the miRNAs that were expressed in each leukocyte cell subtype. Two-way hierarchical clustering on the miRNAs and samples illustrated that miRNA expression profiles of B- and T-cells were very much alike, and that there there were a number of miRNAs which appeared to have an expression profile specific to certain leukocyte cell subtypes. This study will facilitate the identification of microRNAs associated with and contributing to single leukocyte cell subtypes.

overall_design: Peripheral blood leukocytes were extracted, and neutrophils, monocytes, B-cells, T-cells, CD4+ T-cells, and CD8+ T-cells were FACS sorted from total blood from a healthy subject. In order to determine the miRNA expression profile of these cells, RNA was extracted, labeled and hybridized on an Affymetrix miRNA array.

first: R

last: van Eijsden

first: T

last: Ayoubi


title: Chromosomal duplication in the grandifolia-D mutants of Arabidopsis thaliana, tiling array data

first: Nathalie

last: Gonzalez

summary: The number of cells in an organ is a major factor for the determination of organ size. However, genetic basis of cell number determination is not well understood. Three grandifolia-D (gra-D) mutants of Arabidopsis thaliana developed huge leaves containing two- to three-fold increased number of cells of the wild type. Tiling array and microarray analysis of gra-D mutants suggested that genes found in a lower part of chromosome 4 were upregulated, suggesting the occurrence of segmental chromosomal duplications in the gra-D mutants. These region contain positive regulators of cell proliferation such as  AINTEGUMENTA (ANT) and cyclin genes such as CYCD3;1.

overall_design: genomic DNA was extracted using DNeasy plant mini kit (Qiagen) from vegetative part of seedlings  grown in vitro. DNA from  wild type (wt, control) and the 3 grandifolia mutants (gra1-D, gra2-D and gra3-D) were submitted to tiling array hybridization.

first: Gorou

last: Horiguchi

first: Gerrit

middle: T

last: Beemster

first: Dirk

last: Inzé

first: Hirokazu

last: Tsukaya


title: Definitive haplotypes from a collection of complete hydatidiform moles (CHMs)

status: Public on May 12 2009

city: Fukuoka

first: Kenshi

last: Hayashi

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

department: Medical Institute of Bioregulation

country: Japan

institute: Kyushu University

summary:
The haplotype map constructed by the International HapMap Project is a valuable source for the studies of disease genes, population structure, and evolution. In the Project, haplotypes have been inferred from experimentally determined genotypes, and are fairly accurate for Caucasians and Africans since the inference was based on the genotypes of trios. However, the inference for the Asians populations was less accurate, because of the lack of familial information.
Here we assessed how the error in the inference can affect downstream studies, especially the analysis of recent positive selections, by comparing the results of the analyses using the data of HapMap JPT and of definitive haplotypes (DHaplo-DB) determined by us from a collection of Japanese complete hydatidiform moles (CHM), each of which carries a genome derived from a single sperm. We found that the error in JPT was not uniform throughout the genome, and the statistics for recent positive selection was significantly affected.

Keywords: Definitive haplotype determination using CHMs, which carry haploid genomes.

overall_design: 100 CHM samples collected throughout Japan were analyzed by Affymetrix Genechip Mapping 500K Set array.

first: Koichiro

last: Higasa

first: Yoji

last: Kukita

first: Kiyoko

last: Kato

first: Norio

last: Wake

first: Tomoko

last: Tahira


title: SNP analysis AID-low vs AID-high

status: Public on Jul 20 2009

city: Los Angeles

first: Markus

last: Müschen

state: CA

address: 4650 Sunset Blvd

department: Childrens Hospital Los Angeles

institute: University of Southern California

summary: SNP analysis AID-low vs AID-high

overall_design: SNP analysis AID-low vs AID-high


title: Virtual Karyotyping of Androgen Insensitive Prostate Cancer

status: Public on May 09 2009

city: Houston

first: Federico

middle: A

last: Monzon

state: TX

address: 6565 Fannin St., MS205

department: Pathology

institute: The Methodist Hospital Research Institute

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

summary: We investigated chromosomal imbalances in samples from patients with androgen insensitive prostate cancer.

overall_design: 4 archival FFPE tumor samples were analyzed with Affymetrix 250K Nsp SNP microarrays and virtual-karyotype results for PTEN region were compared to PTEN deletion analysis by FISH.

first: Kanishka

last: Sircar

first: Karla

last: Alvarez

first: Jeremy

last: Squire


title: Affymetrix SNP array data for low-grade astrocytoma samples

status: Public on Apr 16 2009

city: London

first: Tim

last: Forshew

address: 4 Newark Street

department: Centre for Neuroscience

country: United Kingdom

institute: Queen Mary's School of Medicine and Dentistry

summary: Copy number analysis of 21 paediatric low-grade astrocytomas identified a discrete copy number gain of 1.9Mb in chromosome band 7q34. The gain was present in 12/14 cerebellar pilocytic astrocytomas. Subsequent analysis of tumour cDNA indentified a novel gene fusion between KIAA1549 and BRAF in these tumours.

overall_design: Copy number analysis of 21 paediatric low-grade astrocytomas using the Affymetrix GeneChip Human Mapping 250K Nsp Array.  This study comprised 14 pilocytic astrocytomas, 4 diffuse astrocytomas, one pilomyxoid astrocytoma, one pilomyxoid glioma and one pleomorphic xanthoastrocytoma. Tumours were compared to the mean of two normal male DNA controls.

first: Ruth

last: Tatevossian

first: Andrew

last: Lawson

first: Tracy

last: Chaplin

first: Bryan

middle: D

last: Young

first: David

middle: W

last: Ellison

first: Denise

last: Sheer


title: Bisulfite Methylation Profiling (BiMP) analysis of met1-3 epigenetic Recombinant Inbred Lines (epiRILs)

status: Public on Apr 23 2009

city: Genève

first: Jon

last: Reinders

state: Genève

address: 30 quai Ernest-Ansermet

department: Department of Plant Biology

country: Switzerland

institute: Universite de Geneve

type: Methylation profiling by genome tiling array

summary:
Epigenomic mapping of DNA methylation polymorphisms segregating within an epigenetic Recombinant Inbred Line population resultant from crossing the wild-type Col-0 and DNA maintenance methyltransferase mutant, met1-3, parental lines. Each line within the epiRIL population was self-fertilized for 7 generations, 10 individual F7 plants were then bulk harvested to create the F8 generation. Here, data files for three DNA methylation profiled epiRIL lines (epi01, epi12, epi28) are deposited. The DNA methylation polymorphisms were determined using the BiMP method with the Affymetrix Arabidopsis Tiling 1.0R array. The main objective for these samples was to create an epigenomic map to analyze the inheritance of DNA methylation polymorphisms within these three epiRIL entries.

Keywords: Bisulfite Methylation Profiling (BiMP) by genome tiling array

overall_design: Each epiRIL entry consists has three replicates hybridizations, using a single channel, creating 9 samples (9 CEL files) within this series. Per sample, DNA was extracted from a bulk of ten F8 individuals and used per hybridization. Each sample and the corresponding hybridization were independent biological replicates. The hybridizations were scanned and analyzed to detect significant differences betwen epiRILs and the parents. Fully informative comparisons that could clearly identify parental origin were used to create DNA methylation marker epigenomic maps.


title: Affymetrix 500K Mapping Array data from ovary tumors

status: Public on May 18 2009

city: South San Francisco

first: Peter

last: Haverty

address: 1 DNA Way

department: Bioinformatics

institute: Genentech, Inc.

summary:
Fifty-seven ovary tumors were profiled for copy-number alterations with the high-resolution Affymetrix 500K Mapping Array.

Keywords: Mapping Array

overall_design: Affymetrix 500K Mapping Array intensity signal CEL files were processed by dChip 2005 (Build date Nov 30, 2005) using the PM/MM difference model and invariant set normalization.  Forty-eight normal samples were downloaded from the Affymetrix website (http://www.affymetrix.com/support/technical/byproduct.affx?product=500k) and analyzed at the same time.  One CEL file for each set (Sty and Nsp) with the median signal intensity across the set was selected as the reference array.   The dChip-normalized signal intensities were converted to log2 ratios and segmented as follows.  For each autosomal probe set, the log2 tumor/normal ratio of each tumor sample was calculated using the average intensity for each probe set in the normal set.  For Chromosome X, the average of the 20 normal female samples was used.   Each probe set was mapped to the genome, NCBI assembly version 36, using annotation provided by the Affymetrix web site.  The log2 ratios were centered to a median of zero and segmented using the GLAD package for the R statistical environment. Copy number was calculated as power(2,log2ratio + 1).

first: Zemin

last: Zhang

first: John

last: Chant


title: Human cleavage stage embryos are chromosomally unstable

status: Public on Apr 26 2009

first: Thierry

last: Voet

address: Herestraat 49

department: Department of Human Genetics

institute: KULeuven

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

summary:
Embryonic chromosome aberrations cause birth defects and reduce human fertility. However, neither their nature nor incidence are known. Here, we develop a method to assess genome-wide copy number variation and loss of heterozygosity in single cells and apply it to screen blastomeres from in vitro fertilized preimplantation embryos. Complex patterns of chromosome-arm imbalances or segmental deletions, duplications or amplifications that were reciprocal in sister blastomeres were detected in a large proportion of the embryos. In addition, aneuploidies and uniparental isodisomies were frequently observed. Since these embryos were derived from young fertile couples, the data indicate that chromosomal instability is common to human embryogenesis.

Keywords: comparative genomic hybridisation

overall_design: In total 180 amplified single cell DNA samples were analyzed by BAC array CGH and 101 of these amplified single cell DNA samples were further analyzed on 250K Nsp I SNP arrays.  19 amplified single cell DNA samples derived from the Epstein Barr virus transformed lymphoblastoid cell lines (EBV-line) were analyzed by BAC array CGH (platform GEO accession number GPL6597). 3 single cell amplified DNA samples from EBV-line [47,XY,+21], 1 single cell amplified DNA sample from EBV-line [46,XY,der(20),t(18;20)(p11.21;p13)], 1 single cell amplified DNA sample from EBV-line [46,X,der(X),t(X;14)(q21.1;q12.2)], 4 single cell amplified DNA samples from EBV-line [46,XX,del(18)(p11.21->pter)], 3 single cell amplified DNA samples from EBV-line [46,XX,del(4)(p16.1->pter)] and 7 single cell amplified DNA samples from EBV-line [47,XXX]. For these single cell BAC array CGH analyses: non-amplified genomic DNA extracted from the blood of a Klinefelter patient (XXY) was used as a reference sample. 1 single cell amplified DNA sample from EBV-line [47,XY,+21] was re-analyzed by BAC array CGH (platform GPL6597) using non-amplified genomic DNA from a male (46,XY). 7 of these 19 amplified single cell DNA samples derived from the Epstein Barr virus transformed lymphoblastoid cell lines (EBV-line) were further analyzed on 250K Nsp I SNP arrays (GEO accession number GPL3718). One single cell amplified DNA sample from EBV-line [47,XY,+21], one single cell amplified DNA sample from EBV-line [46,XY,der(20),t(18;20)(p11.21;p13)], one single cell amplified DNA sample from EBV-line [46,X,der(X),t(X;14)(q21.1;q12.2)] and four single cell amplified DNA samples from EBV-line [46,XX,del(18)(p11.21->pter)].  146 amplified single blastomere DNA samples derived from 3-day-old and 4-day-old human embryos were analyzed by BAC array CGH (144 single blastomeres on platform GPL6597 and 2 on a custom-made platform 4K3). Non-amplified genomic DNA extracted from the blood of a Klinefelter patient (XXY) was used as a reference sample. 86 of these 146 amplified single blastomere DNA samples were further analyzed on 250K Nsp I SNP arrays (platform GPL3718).  15 human fertilized oocytes in the pronuclear stage were analyzed by BAC array CGH (platform GPL6597). Non-amplified genomic DNA extracted from the blood of a Klinefelter patient (XXY) was used as a reference sample. 8 of these 15 were further analyzed on 250K Nsp I SNP arrays (platform GPL3718).  Apart from these 180 single cell amplified DNA samples, also 4 non-amplified genomic DNA samples, respectively from EBV-lines [47,XY,+21], [46,XY,der(20),t(18;20)(p11.21;p13)], [46,X,der(X),t(X;14)(q21.1;q12.2)] and [46,XX,del(18)(p11.21->pter)], were analyzed by BAC array CGH and 250K Nsp I SNP arrays. Non-amplified genomic DNA extracted from the blood of a Klinefelter patient (XXY) was used as a reference sample for BAC array CGH.

first: Evelyne

last: Vanneste

first: Cédric

last: Le Caignec

first: Michèle

last: Ampe

last: Konings

first: Cindy

last: Melotte

first: Sophie

last: Debrock

first: Mikka

last: Viikkula

first: Frans

last: Schuit

first: Jean-Pierre

last: Fryns

first: Geert

last: Verbeke

first: Thomas

last: D'Hooghe

first: Yves

last: Moreau

first: Joris

last: Vermeesch


title: A20 IN MARGINAL ZONE LYMPHOMAS

status: Public on Apr 01 2009

city: Bellinzona

first: Francesco

last: Bertoni

state: Ticino

address: Via V. Vela 6

department: Lymphoma & Genomics Research Program

institute: IOR

summary:
Unique and shared cytogenetic abnormalities have been documented for marginal zone lymphomas (MZLs) arising at different sites. Recently, homozygous deletions of the chromosomal band 6q23, involving the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) gene, a negative regulator of NF-kappa B, were described in ocular adnexal MZL, suggesting a role for A20 as a tumor suppressor in this disease entity. Here, we investigated inactivation of A20 by DNA mutations or deletions in a panel of extranodal (EMZL), nodal (NMZL) and splenic (SMZL) MZLs. Inactivating mutations encoding truncated A20 proteins were identified in 6/32 (18.8%) MZLs, including 3/11 (27.3%) EMZLs, 2/9 (22.2%) NMZLs, and 1/12 (8.3%) SMZLs. Two additional unmutated non-splenic MZLs also showed mono- or biallelic A20 deletions by FISH and/or array-CGH. Thus, A20 loss by both somatic mutations and/or deletions represents a common genetic aberration across all MZL subtypes, which may contribute to lymphomagenesis by inducing constitutive NF-kappa B activation.

Keywords: Genome variation profiling by SNP array

overall_design: 27 MZL samples. No technical replications.

first: Andrea

last: Rinaldi

first: Ivo

last: Kwee

first: Urban

last: Novak

first: Govind

last: Bhagat


title: Genomic profiling data of 19 pediatric lympohoblastic lymphoma patients

status: Public on Feb 01 2009

first: Roland

last: Kuiper

summary:
Lymphoblastic lymphoma (LBL) is one of the most frequent occurring pediatric non-Hodgkin lymphomas. In the WHO classification scheme pediatric LBL is considered to be the same disease entity as pediatric acute lymphoblastic leukemia (ALL). However, it is unclear whether the genetic basis of pediatric LBL development is similar to that of pediatric ALL. We performed genome-wide analyses of copy number aberrations in 12 T-LBL and 7 precursor B-cell LBL pediatric cases using high-resolution SNP-based array CGH. Similar to what previously has been found in T-ALLs, T-LBLs exhibited recurrent deletions of the CDKN2A locus, occurring in 92% of the cases. Additionally, we detected deletions of RB1 (16%), duplications of MYB (16%) and an amplification of ABL1 in one case. These results show that, similar to T-ALL,  the genomic alterations in T-LBL predominantly target genes involved in cell cycle progression. The majority of precursor B-cell LBLs was characterized by high-hyperdiploidy (71%), and showed high resemblance with high-hyperdiploid precursor B-cell ALLs.  These results show that, similar to T-ALL,  the genomic alterations in T-LBL predominantly target genes involved in cell cycle progression and that high-hyperdiploidy is a commen event in B-LBL. Taken together, our data suggest that pediatric LBLs and ALLs exhibit similar genomic abnormalities within confined immunophenotypic and cytogenetic subgroups, but that the representations of these subgroups differs between the two entities.
Copy number detection was performed using CNAG2.0 software, Reference genomes are included in this data set

Keywords: comparative genome hybridization

overall_design: Genomic DNA from 19 Lymph node or testis was hybridized on Affymetrix Nsp SNP-based arrays according to manufacturer's procedures

first: Margit

last: Schraders

first: Simon

last: vanReijmersdal

first: Ad

last: GeurtsvanKessel

first: Johan

last: M.van Krieken

first: Peter

last: Hoogerbrugge


title: Expression data for drought-, cold, high-salinity and ABA treatment in Arabidopsis plants

status: Public on Nov 19 2008

city: Yokohama

first: Motoaki

last: Seki

address: 1-7-22, Suehiro-cho, Tsurumi

institute: RIKEN CSRS

type: Expression profiling by genome tiling array

summary:
We applied the tiling arrays to study the Arabidopsis whole-genome transcriptome under drought, cold, high-salinity and ABA treatment conditions and idenfied many stress- or ABA- responsive putative functional RNAs and fully-overlapping sense-antisense transcripts in Arabidopsis genome.
Keywords: stress response

overall_design: Two-week-old Arabidopsis plants grown on the agar plates were subjected to the stress- or ABA- treatments. The total RNA was prepared from the treated- and  untreated- plants, and used for the microarray hybridization. Three replicative hybridization experiments for each strand array were carried out using the independent biological RNA samples.

first: Akihiro

last: Matsui

first: Junko

last: Ishida

first: Taeko

last: Morosawa

first: Yoshiki

last: Mochizuki

first: Norio

last: Kobayashi

first: Kazuo

last: Shinozaki

first: Tetsuro

last: Toyoda


title: Genomic profiles of diffuse large B-cell lymphomas

first: Francesco

last: Bertoni

summary:
Despite recent therapeutic improvements, the clinical course of diffuse large B-cell lymphoma (DLBCL) still differs considerably among patients. We conducted this retrospective multi-centre study to evaluate the impact of genomic aberrations detected using a high-density genome wide-single nucleotide polymorphism-based array on clinical outcome in a population of DLBCL patients treated with R-CHOP-21 (rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21 d). 167 DNA samples were analysed using the GeneChip Human Mapping 250K NspI. Genomic anomalies were analysed regarding their impact on the clinical course of 124 patients treated with R-CHOP-21. Unsupervised clustering was performed to identify genetically related subgroups of patients with different clinical outcomes. Twenty recurrent genetic lesions showed an impact on the clinical course. Loss of genomic material at 8p23.1 showed the strongest statistical significance and was associated with additional aberrations, such as 17p- and 15q-. Unsupervised clustering identified five DLBCL clusters with distinct genetic profiles, clinical characteristics and outcomes. Genetic features and clusters, associated with a different outcome in patients treated with R-CHOP, have been identified by arrayCGH.
DNA copy number profiling by SNP array.

overall_design: DNA from DLBCL patient samples. No technical replications.

first: Marta

last: Scandurra

first: Andrea

last: Rinaldi

first: Ivo

last: Kwee


title: A gene expression signature associated with K-Ras addiction reveals regulators of EMT and tumor cell survival

status: Public on Mar 06 2009

city: Charlestown

first: Patricia

last: Greninger

state: MA

department: Center for Molecular Therapeutics

institute: Massachusetts General Hospital Cancer Center

type: Genome binding/occupancy profiling by SNP array

summary: K-Ras mutations occur frequently in epithelial cancers. Using shRNAs to deplete K-Ras in lung and pancreatic cancer cell lines harboring K-Ras mutations, two classes were identified—lines that do or do not require K-Ras to maintain viability.  Comparing these two classes of cancer cells revealed a gene expression signature in K-Ras-dependent cells, associated with a well-differentiated epithelial phenotype, which was also seen in primary tumors. Several of these genes encode pharmacologically tractable proteins, such as Syk and Ron kinases and integrin beta6, depletion of which induces epithelial-mesenchymal transformation (EMT) and apoptosis specifically in K-Ras-dependent cells. These findings indicate that epithelial differentiation and tumor cell viability are associated, and that EMT regulators in “K-Ras-addicted” cancers represent candidate therapeutic targets.

overall_design:
Expression analysis: 40 Samples representing K-Ras mutant cancer cell lines derived from various tissue types were hybridized to the Affymetrix GeneChip Human X3P Array.

Copy number analysis: 10 samples representing K-Ras mutant cancer cell lines were hybridized to the Affymetrix Mapping 500K Set Arrays (250K_Nsp_SNP and 250K_Sty2_SNP).

Reference data included 63 randomly chosen female samples (supplementary file Sing_etal_CopyNumber_NormalSamples.txt) from the HapMap project Affy 500K SNP data (http://www.hapmap.org/downloads/raw_data/affy500k).

first: Anurag

last: Singh

first: Jeffrey

last: Settleman


title: Genotyping data from 54 patients with deficit schizophrenia

status: Public on Oct 22 2008

first: Joris

middle: Andre

last: Veltman

summary:
Schizophrenia is a severe psychiatric disease with complex etiology, affecting approximately one percent of the general population. Most genetic studies so far focused on disease association with common genetic variation such as single nucleotide polymorphisms, but recently it has become apparent that large-scale genomic copy number variants (CNVs) are involved in disease development as well.
To assess the role of rare CNVs in schizophrenia, we screened 54 patients with deficit schizophrenia using Affymetrix’ GeneChip 250K SNP arrays.
Keywords: genomic hybridisation

overall_design: We hybridized genomic DNA of 54 patients with deficit schizophrenia to Affymetrix' GeneChip 250K SNP (Nsp) arrays, and identified genome-wide CNV using the Copy Number Analyzer for Affymetrix GeneChip (CNAG v2.0) software, which uses a Hidden Markov Model (HMM) algorithm to calculate copy numbers.

first: Jayne

last: Hehir-Kwa


title: Expression data in Arabidopsis rdr2-1 and ddc (drm1-1drm2-2cmt3-11) mutants.

status: Public on Oct 23 2008

first: Motoaki

last: Seki

summary:
We applied the tiling arrays to study the Arabidopsis whole-genome transcriptome in Arabidopsis rdr2-1 and ddc mutants.

Keywords: untreated condition

overall_design: The total RNA was prepared from 15-day-old Arabidopsis plants (wild type (WT), rdr2-1 and ddc) and used for the microarray hybridization. Three replicative hybridization experiments for each strand array were carried out using the independent biological RNA samples.

first: Yukio

last: Kurihara

first: Makiko

last: Kawashima


title: Genotyping data from 120 trios with unexplained mental retardation

summary:
In the study we present a multicenter study in which three European diagnostic centres assessed the use of Affymetrix Mapping 500k SNP arrays for molecular karyotyping in patients with mental retardation. Each centre tested DNA from 40 patients with unexplained mental retardation together with their parents. In addition, 38 DNA samples containing known submicroscopic copy number variations (CNVs) were run for validation purposes

Keywords: genomic hybridisation

overall_design: We performed a validation experiement where genomic DNA of 38 patients with mental retardation  was hybridized onto Affymetrix' GeneChip 250K SNP (Nsp) arrays, and identified genome-wide CNVs. An application study was then performed where 40 trios from 3 different centres where hybrized and CNVs identified.

first: Michael

last: Bonin

first: Dominic

last: McMullan


title: Copy number analysis of human glioblastoma multiforme

status: Public on Jan 05 2009

city: Washington

first: David

last: Solomon

state: DC

address: 3970 Reservoir Rd, N.W.

department: Oncology

institute: Georgetown University School of Medicine

summary:
Copy number analysis of human GBM samples were performed, and a high frequency of deletions of the PTPRD gene on chromosome 9p23-24.1 were identified.

Keywords: SNP microarray, glioblastoma multiforme, copy number, amplification, deletion

overall_design: Genomic DNA from 58 GBM tumor samples were hybridized to Affymetrix 250K NspI Gene Chip Arrays and analyzed by dChip using the hg17 genome assembly.

first: Habtom

last: Ressom

first: Todd

last: Waldman


title: Expression data in Arabidopsis upf1-1 and upf3-1 mutants.

status: Public on Jan 14 2009

summary:
We applied the tiling arrays to study the Arabidopsis whole-genome transcriptome in Arabidopsis upf1-1 and upf3-1 mutants.

Keywords: untreated condition

overall_design: Fifteen-day-old Arabidopsis plants grown on the agar plates. The total RNA was prepared from 15-day-old Arabidopsis plants (wild type (WT, UPF), upf1-1 and upf3-1) and used for the microarray hybridization. Three replicative hybridization experiments for each strand array were carried out using the independent biological RNA samples.

first: Akihiro

last: Matsui

first: Junko

last: Ishida

first: Maho

last: Tanaka

first: Taeko

last: Morosawa

first: Yoshiki

last: Mochizuki

first: Kazuo

last: Shinozaki

first: Tetsuro

last: Toyoda


title: Integrative genomic approach reveals expression of intronic miR-335, miR-342, and miR-561 in multiple myeloma

status: Public on Nov 11 2008

city: MILAN

first: Luca

last: Agnelli

address: Venezian 1

department: Department of Advanced Diagnostics

country: Italy

institute: IRCCS Istituto Nazionale dei Tumori

summary:
The role of microRNAs (miRNAs) in multiple myeloma (MM) has yet to be fully elucidated. To identify miRNAs that are potentially deregulated in MM, we investigated those mapping within transcription units, based on evidence that intronic miRNAs are frequently coexpressed with their host genes. To this end, we monitored host transcript expression values in a panel of 20 human MM cell lines (HMCLs) profiled on Affymetrix U133A oligonucleotide microarrays and focused on transcripts whose expression varied significantly across the dataset. We identified transcripts specific to six miRNA host genes (CCPG1, GULP1, EVL, TACSTD1, MEST, and TNIK) whose average changes in expression varied at least 2-fold from the mean of the examined dataset. We evaluated the expression levels of the corresponding intronic miRNAs by quantitative real-time RT-PCR. There was a significant correlation between the expression levels of MEST, EVL, and GULP1 and those of the corresponding miRNAs miR-335, miR-342-3p, and miR-561, respectively. Genome-wide profiling of the 20 HMCLs with the Affymetrix GeneChip human mapping 250K array set indicated that the increased expression of the three host genes and their corresponding intronic miRNAs was not correlated with local copy number variations. Notably, miRNAs and their host genes were overexpressed in a fraction of primary tumors with respect to normal plasma cells; however, this finding was not correlated with known molecular myeloma groups. The predicted putative miRNA targets, as well as the transcriptional profiles associated with the primary tumors, suggest that MEST/miR-335 and EVL/miR-342-3p may play a role in plasma cell homing and/or interactions with the bone marrow microenvironment. Our data support the idea that intronic miRNAs and their host genes are regulated dependently, and may contribute to the understanding of their biological roles in cancer. To our knowledge, this is the first evidence of deregulated miRNA expression in MM, providing insights that may lead to the identification of new biomarkers and altered molecular pathways of the disease.

Keywords: integrative genomic analysis of miR-335, miR-342, and miR-561 in multiple myeloma

overall_design: This series of microarray experiments contains the genome-wide profiles of 20 HMCLs. 250 nanograms of genomic DNA was processed and, in accordance with the manufacturer's protocols, 90 micrograms of fragmented biotin-labelled DNA were hybridized on GeneChip® Human Mapping 250K NspI Arrays (Affymetrix Inc.). The arrays were scanned using the GeneChip® Scanner 3000 7G. The images were acquired using Affymetrix GeneChip® Operating Software (GCOS version 1.4). Copy number values for individual SNPs were extracted and converted from CEL files into signal intensities using GTYPE 4.1 and Affymetrix Copy Number Analysis Tool (CNAT 4.0.1) softwares. Raw data were extracted using the Hidden Markov Model Genomic Smoothing window was set to 0. After the preprocessing, piecewise constant estimates of the underlying local DNA CN variation was calculated using the DNA copy Bioconductor package, which looks for optimal breakpoints using circular binary segmentation (CBS).

first: Domenica

last: Ronchetti

first: Marta

last: Lionetti

first: Laura

last: Mosca

first: Adrian

last: Andronache

first: Sonia

last: Fabris

first: Giorgio

last: Lambertenghi-Deliliers

first: Antonino

last: Neri


title: Genomic profiling of prostate cancer in African-American patients

status: Public on Mar 03 2009

first: Chad

last: Creighton

address: One Baylor Plaza, Mail Stop: BCM305

department: Biostatistics, Ducan Cancer Center

institute: Baylor College of Medicine

summary:
African-Americans with prostate cancer tend to have a more aggressive form of the disease, as compared to their Caucasian counterparts. Nevertheless, African-Americans tend to be underrepresented in most molecular profiling studies of prostate cancer.  To investigate DNA copy number alterations (CNAs) in prostate cancer from a cohort of African-Americans, we profiled 20 tumors (each with paired normal) for 500,000 SNPs.

Keywords: tumor-normal comparison

overall_design: Profiles were generated on two Affymetrix array chips: Nsp and Sty, each with ~250K SNPs represented.  In all, 20 tumors and 20 paired normal samples were profiled, 40 profiles in all.  Each tumor was centered on its corresponding normal pair to define copy number alterations (CNA) in that tumor.

first: Michael

last: Ittmann

first: Mustafa

last: Ozen

first: Dror

last: Berel


title: Screening for copy-number alterations and LOH in CLL - a comparative study of four microarray platforms

status: Public on Dec 10 2008

city: Uppsala

first: Richard

last: Rosenquist Brandell

address: Rudbeck Laboratory

department: Genetics and Pathology

country: Sweden

institute: Uppsala University

summary: Screening for gene copy-number alterations (CNAs) has improved by applying genome-wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high-resolution platforms: BAC arrays (32K), oligonucleotide arrays (185K, Agilent), and two SNP arrays (250K, Affymetrix and 317K, Illumina). Cross-platform comparison revealed 29 concordantly detected CNAs, including known recurrent alterations, which confirmed that all platforms are powerful tools when screening for large aberrations. However, detection of 32 additional regions present in 2-3 platforms illustrated a discrepancy in detection of small CNAs, which often involved reported copy-number variations. LOH analysis revealed concordance of mainly large regions, but showed numerous, small nonoverlapping regions and LOH escaping detection. Evaluation of baseline variation and copy-number ratio response showed the best performance for the Agilent platform and confirmed the robustness of BAC arrays. Accordingly, these platforms demonstrated a higher degree of platform-specific CNAs. The SNP arrays displayed higher technical variation, although this was compensated by high density of elements. Affymetrix detected a higher degree of CNAs compared to Illumina, while the latter showed a lower noise level and higher detection rate in the LOH analysis. Large-scale studies of genomic aberrations are now feasible, but new tools for LOH analysis are requested.

overall_design: 10 chronic lymphocytic leukemia (CLL) samples was analyzed using four different high-resolution platforms: 32K BAC arrays, 185K Agilent oligonucleotide arrays, 250K Affymetrix SNP arrays and 317K Illumina SNP arrays.

first: Rebeqa

last: Gunnarsson

first: Johan

last: Staaf

first: Mattias

last: Jansson

first: Anne-Marie

last: Ottesen

first: Hanna

last: Göransson

first: Ulrika

last: Liljedahl

first: Ulrik

last: Ralfkiær

first: Mahmoud

last: Mansouri

first: Anne-Mette

last: Buhl

first: Karin

last: Ekström Smedby

first: Henrik

last: Hjalgrim

first: Ann-Christine

last: Syvänen

first: Ake

last: Borg

first: Anders

last: Isaksson

first: Jesper

last: Jurlander

first: Gunnar

last: Juliusson

last: Rosenquist


title: Affymetrix 500K Mapping Array data from breast tumors

status: Public on Mar 17 2008

first: Peter

last: Haverty

summary:
Fifty-one breast tumors were profiled for copy-number alterations with the high-resolution Affymetrix 500K Mapping Array. Combined analysis of the prevalence and amplitude of copy-number alterations defined regions of recurrent gain or loss. Gains were most frequently observed on chromosomes 1, 8, 10, 11, 13, 15, 17, and 20. Losses were most frequent on chromosomes 3, 6, 11, 13, 14, 16, and 17. Compared with previous lower-resolution data, our analysis provided significantly more precise boundaries for frequently altered regions, greatly reducing the number of potential alteration-driving genes.
Keywords: Mapping Array

overall_design: Affymetrix 500K Mapping Array intensity signal CEL files were processed by dChip 2005 (Build date Nov 30, 2005) using the PM/MM difference model and invariant set normalization.  Forty-eight normal samples were downloaded from the Affymetrix website (http://www.affymetrix.com/support/technical/byproduct.affx?product=500k) and analyzed at the same time.  One CEL file for each set (Sty and Nsp) with the median signal intensity across the set was selected as the reference array.   The dChip-normalized signal intensities were converted to log2 ratios and segmented as follows.  For each autosomal probe set, the log2 tumor/normal ratio of each tumor sample was calculated using the average intensity for each probe set in the normal set.  For Chromosome X, the average of the 20 normal female samples was used.   Each probe set was mapped to the genome, NCBI assembly version 35, using annotation provided by the Affymetrix web site.  The log2 ratios were centered to a median of zero and segmented using the GLAD package for the R statistical environment. Copy number was calculated as power(2,log2ratio + 1).

first: Jane

last: Fridlyand

first: Li

last: Li

first: Gad

last: Getz

first: Rameen

last: Beroukhim

first: Scott

last: Lohr

first: Thomas

last: Wu

first: Guy

last: Cavet

first: Zemin

last: Zhang

first: John

last: Chant


title: Adult and adolescent acute lymphoblastic leukemia

status: Public on Apr 10 2008

first: Kajsa

last: Paulsson

address: John Vane Science Centre, Charterhouse Square

department: Medical Oncology Centre

institute: Cancer Research UK

summary:
We present here a genome-wide map of abnormalities found in diagnostic samples from 45 adults and adolescents with acute lymphoblastic leukemia (ALL). 500K single nucleotide polymorphism (SNP) array analysis uncovered frequent genetic abnormalities, with cryptic deletions constituting half of the detected changes, implying that microdeletions are a characteristic feature of this malignancy. Importantly, the pattern of deletions resembled that recently reported in pediatric ALL, suggesting that adult, adolescent, and childhood cases may be more similar on the genetic level than previously thought. Thus, 70% of the cases displayed deletion of one or more of the CDKN2A, PAX5, IKZF1, ETV6, RB1, and EBF1 genes. Furthermore, several genes not previously implicated in the pathogenesis of ALL were identified as possible recurrent targets of deletion. In total, the SNP array analysis identified 367 genetic abnormalities not corresponding to known copy number polymorphisms, with all but two cases (96%) displaying at least one cryptic change. This SNP array study is the first to specifically address adult and adolescent ALL, and the resolution level is the highest used to date to investigate a malignant hematologic disorder. Our findings provide insights into the leukemogenic process and may be clinically important in adult and adolescent ALL. Most importantly, we report that microdeletions of key genes appear to be a common, characteristic feature of ALL that is shared between different clinical, morphological, and cytogenetic subgroups.
Keywords: Genomic analysis of acute lymphoblastic leukemia samples

overall_design: Diagnostic samples from 45 adult or adolescent acute lymphoblastic leukemia samples were analyzed with the Affymetrix 250K Nsp, 250K Sty, and 10K 2.0 SNP arrays. Ten samples from leukemia patients in remission were used as normal controls. Copy number changes were analyzed with the NSP and STY arrays, and regions of uniparental disomies with the 10K arrays.

first: Jean-Baptiste

last: Cazier

first: Finlay

last: MacDougall

last: Stevens

first: Irina

last: Stasevich

first: Nikoletta

last: Vrcelj

first: Tracy

last: Chaplin

first: Debra

last: Lillington

first: T

last: Lister

first: Bryan

last: Young


title: X-inactivation in hESCs

status: Public on Feb 19 2008

first: Yin

last: Shen

address: 695 Charles E. Young Dr.

institute: UCLA

summary:
X chromosome inactivation (XCI) is a dosage compensation mechanism in female cells to regulate X-linked gene expression.  We report here that subcultures from established lines of female hESCs displayed variations (0-100%) in the expression of XCI markers such as XIST RNA coating and enrichment of histone H3 lysine 27 trimethylation (H3K27me3) on inactive X chromosome.   Surprisingly, regardless of the presence or absence of XCI markers in different cultures, all female hESCs we examined (H7, H9, and HSF6 cells) exhibit a mono-allelic expression pattern for a majority of X-linked genes.  Our results suggest that these established female hESCs have completed XCI during the process of derivation and/or propagation, and the XCI pattern of lines we investigated is already non-random.  However, XIST gene expression in subsets of female hESCs is unstable and subject to epigenetic silencing through DNA methylation.  Concomitant with the loss of XCI markers including XIST expression and H3K27me3, approximately 12% of X-linked CpG islands become hypomethylated and a subset of previously silenced X-linked alleles are reactivated, resulting a significant elevation of gene expression dosage. Because changes in dosage compensation of X-linked genes could impair somatic cell function, we propose that XCI status should be routinely checked in subcultures of female hESCs, with cultures displaying XCI markers better suited for use in regenerative medicine.
Keywords: Genotyping, gene expression and DNA methylation

overall_design: We used Affymetrix Genotyping array for looking for X-linked SNPs with HSF6, H7 and H9 genomic DNA, Agilent Gene expression array for comparing gene expression patten changes between HSF6 hESCs with X-inactiation and HSF6 hESCs without X-inactivation (3 repeats). Finally, mDIP-Chip method was used to detect X-linked CpG island methylation changes differences between hESCs with X-inactivation and hESCs without X-inactivation using Agilent CpG island array (3 repeats, and one of them has dye swap)

first: Youko

last: Matsuno

first: Shaun

last: Fouse

first: Nagesh

last: Rao

first: Sierra

last: Root

first: Ren-he

last: Xu

first: Matteo

last: Pellegrini

first: Arthur

last: Riggs

first: Guoping

last: Fan


title: The Complete Genome of a Single Individual by Massively Parallel DNA Sequencing

status: Public on Feb 29 2008

first: Omar

last: Alvi

address: 1 Baylor Plaza

department: Human Genome Sequencing Center

summary:
The association of genetic variation with disease and drug response, together with improvements in nucleic acids technologies, has given great optimism for the impact of 'genomic medicine'.  However, the formidable size of the diploid human genome has prevented the routine application of sequencing methods to deciphering complete individual human genomes, and has so far limited the realization of the full potential of genomics for science and human health. Working towards the goal of harnessing the power of genomics, we sequenced the diploid genome of a single individual, Dr. James D. Watson, using a massively-parallel method of sequencing in picoliter size reaction vessels. Here we report the results of genotyping the subject's DNA using an Affymetrix 500k GeneChip as well as copy number variations as reported by Agilent 244k comparative genomic hybridization arrays.
Keywords: Genotyping, copy number variation (CNV), aCGH

overall_design:
Affymetrix Gene Chip 500: Duplicate genomic DNA samples from JW's lymphocytes, 250 ng each, were annealed to the Affymetrix 250K NspI and 250K StyI arrays according to the manufacturer's protocol. Genotypes were determined using the Bayesian Robust Linear Model with Mahalanobis distance classifier (BRLMM) algorithm provided by Affymetrix in the GeneChip Genotyping Analysis software v. 4.0.
Agilent 244k Whole Human Genome Oligo Microarray: 2 ug of DNA from experimental (JW) and reference samples were processed according to Agilent protocols with some modification. Reference samples were procured from the standard reference Caucasian male, Kleberg Cytogenetics Laboratory, Baylor College of Medicine (Chip 1) and Coriell number NA10851 (Chip 2).

first: David

last: Wheeler

first: Maithreyan

last: Srinivasan

first: Michael

last: Egholm

first: Yufeng

first: Lei

last: Chen

first: Amy

last: McGuire

first: Wen

last: He

first: Yi-Ju

first: Vinod

last: Makhijani

first: G

last: Roth

first: Xavier

last: Gomes

first: Karrie

last: Tartaro

first: Faheem

last: Niazi

first: Cynthia

middle: L

last: Turcotte

first: Gerard

last: Irzyk

first: James

last: Lupski

first: Craig

last: Chinault

first: Xing-zhi

last: Song

first: Yue

last: Liu

first: Lynne

last: Nazareth

first: Xiang

last: Qin

first: Donna

last: Muzny

first: Marcel

last: Margulies

first: George

last: Weinstock

first: Richard

last: Gibbs

first: Jonathan

last: Rothberg


title: Analysis of copy number change in cord lining epithelial cells after phage integrase mediated genomic integration.

status: Public on Sep 01 2008

city: Singapore

first: Jaichandran

last: Sivalingam

address: 11 Hospital Drive

department: Division of Medical Sciences

country: Singapore

institute: National Cancer Center

summary: The two obstacles that impede a wider application of genetically modified cells expressing therapeutic transgenes for ex vivo gene therapy are the immune mediated rejection of the transplanted cells, combined with their potential to cause iatrogenic oncogenesis. In this study we describe a new cellular vehicle for this form of therapy, termed the cord lining epithelial cell (CLEC). CLECs are derived from the human amnion and incorporate many of the immunoregulatory functions associated with the fetal/maternal interface. We show that CLECs can be safely transfected by phage φC31 integrase to accomplish site-specific integration of a therapeutic human transgene. We also show that transplanted CLECs are not oncogenic in vivo and can be maintained in immunocompetent mice where acute xeno-rejection rapidly destroys other human cell types. Finally, we demonstrate the utility of CLECs for ex vivo gene therapy by delivering human coagulation factor 8 to mice with Hemophilia A.

overall_design: High-resolution copy number profiling was performed on genomic DNA of untreated (GSM315546 and GSM315713) and phage integrase modified CLECs (GSM315974 and GSM316895) using the Human Mapping 500K Array Set (Affymetrix) and the data analyzed using GeneChip Chromosome Copy Number Analysis Tool. Regions of copy number gain or loss were defined as having 3 consecutive SNPs concordant for significant copy number abnormalities. Log2 signal intensity ratios >0.3 and <-0.3 were criteria for significant copy number gain and loss, respectively.


title: Highly integrated epigenome maps in Arabidopsis - methylcytosine immunoprecipitation

status: Public on Apr 21 2008

city: La Jolla

first: Joseph

last: Ecker

address: 10010 North Torrey Pines Road

department: Genomic Analysis Laboratory

institute: HHMI-Salk-Institute

type: Genome binding/occupancy profiling by genome tiling array

summary:
Part of a set of highly integrated epigenome maps for Arabidopsis thaliana.
Keywords: methylcytosine ChIP-chip on tiling array

overall_design: Identification of cytosine DNA methylation by methylcytosine immunoprecipitation and whole-genome oligonucleotide tiling microarrays for wildtype Columbia-0.

first: Ryan

last: Lister

first: Ronan

middle: C

last: O'Malley

first: Julian

last: Tonti-Filippini

first: Brian

last: Gregory

first: Charles

last: Berry

first: A

last: Millar


title: High-resolution genetic analysis of cancer cell lines with near normal karyotypes

status: Public on Mar 15 2008

first: Xueying

last: Mao

address: Charterhouse Square

institute: Queen Mary

summary:
Cancer development is associated with multiple genetic alterations and genomic instability either at the chromosomal or base pair level is generally thought to underlie these changes.  However, it is still unknown whether genetic instability is absolutely required for tumorigenesis. Here we investigated the genomic instability status of four cytogenetically stable diploid cell lines CAL51, SK-UT-1B, A204 and CH1. We applied high resolution 500K single nucleotide polymorphism (SNP) array analysis and found that all the four cell lines have some sub-microscopic genomic copy number changes. Interestingly, there were many more sub-microscopic chromosome alterations in A204 and CH1 than in CAL51 and SK-UT-1B. Twenty-four-color fluorescence in situ hybridization (FISH) was used to analyse a large number of metaphases from CAL51, SK-UT-1B and CH1 cells. The rate of de novo chromosome rearrangements was significantly higher in CH1 than CAL51 and SK-UT-1B. Although this increased rate did not lead to many clonal cytogenetically apparent chromosome alterations in CH1 cells, it is consistent with a first step towards chromosomal instability. It is more striking that both cell lines CAL51 and SK-UT-1B which have a similar de novo chromosomal change rate to that of normal lymphocytes were microsatellite instability positive by BAT-26 microsatellite analysis. This study further strengths the current concept that genomic instability is associated with tumor development.
Keywords: DNA copy number changes

overall_design: DNA from A204, CH1, CAL51 and SK-UT-1B were analyzed by Affymetrix Genechip Mapping 500K Set array. Data were compared with normal samples from HAPMAP database.

first: Bryan

last: Young

first: Tracy

last: Chaplin

first: Janet

last: Shipley

first: Yong-Jie

last: Lu


title: Genome-wide, High Resolution DNA Methylation Profiling Using Bisulfite-Mediated Cytosine Conversion

status: Public on Nov 30 2007

first: Jon

last: Reinders

summary:
We developed a genome-wide DNA methylation profiling technology that determines methylation patterns using small amounts of starting material. This process involves a novel amplification step for DNA subjected to bisulfite-mediated cytosine conversion and generates highly reproducible datasets with low technical variation.
The technology, named BiMP (for Bisulfite Methylation Profiling), is more cost-effective than mC immunoprecipitation techniques (mCIP) and can be applied to as little as 100 ng of Arabidopsis DNA. It is anticipated that this technology can be applied to mammalian genomes and may allow methylation profiling of a small number of physiologically uniform cells.
Keywords: bisulfite DNA methylation profiling, Arabidopsis, methylation polymorphisms, met1-3,

overall_design: This experiment compared bisulfite-treated entries of the wild type Columbia and the DNA maintenance methyltransferase mutant, met1-3, using non-treated genomic DNA as a reference control.  Per entry, the three biological replicate bisulfite-treated DNA files and the three biological replicate non treated DNA files were selected as the treatment and control group files, respectively, in a two sample comparison analysis using quantile normalization of both groups together. The resulting Col_BS+ and met1-3_BS+ BAR files, for the above two-sample comparisons, were loaded into IGB (Affymetrix) for analysis of differentially methylated regions.

first: Céline

last: Vivier

first: Grégory

last: Theiler

first: Didier

last: Chollet

first: Patrick

last: Descombes

first: Jerzy

last: Paszkowski


title: Genome-wide SNP Array Identification of Genetic Alterations in Cervical Cancer

status: Public on Jun 04 2008

city: New York

first: Murty

last: Vundavalli

state: NY

address: 1130 St Nicholas Ave

institute: Columbia University Medical Center

summary:
Recurrent karyotypic abnormalities are a characteristic feature of cervical cancer (CC) cells, which may result in deregulated expression of important genes that contribute to tumor initiation and progression. To examine the role of genomic copy number alterations, we surveyed genetic lesions in CC utilizing single nucleotide polymorphism (SNP) array. We identified specific genetic alterations associated with CC. These data will be useful in identification of target altered genes, novel markers for predicting high risk precancerous lesions to invasive cancer, comparison of copy number alterations with gene expression changes can provide gene targets for pharmacologic intervention. We demonstrate specific regions of gene amplification (e.g., 11q22), copy number gains (e.g., 3q, 5p, and 20q), and deletions (e.g., 2q, 11q23) in the present study, which forma a framework for identification of critical genes in CC tumorigenesis.
Keywords: Cervical cancer, copy number alterations, HPV type, gene amplification

overall_design: We utilized Affymetrix 250K NspI SNP chip for copy number analysis on 7 normal cervical squamous epithelial samples as controls and 85 cervical cancer specimens. The cervical cancer specimens include 9 cervical cancer cell lines and 85 primary tumors. Eight of the primary tumors analyzed as replicates. Primary tumors consist of various stages of invasive cancer and HPV status of all tumors and cell lines is also included.

first: Vundavalli

last: Murty

first: Luigi

last: Scotto

first: Arias-Pulido

last: Hugo

first: Gopeshwar

last: Narayan

first: Mahesh

last: Mansukhani

first: Achim

last: Schneider


title: Virtual-Karyotyping with SNP microarrays in morphologically challenging renal cell neoplasms

status: Public on Mar 13 2009

first: Federico

last: Monzon

address: 6565 Fannin St., MS205

institute: The Methodist Hospital Research Institute

summary: Genetic lesions characteristic for RCC subtypes can be identified by virtual karyotyping with SNP microarrays. In this study, we examined whether virtual karyotypes could be used to better classify a cohort of morphologically challenging/unclassified RCC.

overall_design: Tumor resection specimens from 17 patients were profiled by virtual karyotyping with Affymetrix 10K 2.0 or 250K Nsp SNP Mapping arrays and were also evaluated independently by a panel of seven genito-urinary pathologists. Tumors were classified by the established pattern of genomic imbalances based on a reference cohort of 98 cases with classic morphology and compared to the morphologic diagnosis of the pathologist panel. In 3 cases, samples from areas with different morphologic appearance were also tested (n=5).

first: Hyun-Jung

last: Kim

first: Karla

last: Alvarez

first: Steven

middle: S

last: Shen


title: Global variation of copy number in the human genome_COMM

status: Public on Sep 30 2006

city: Santa Clara

first: Fan

address: 3420 Central Expressway

institute: Affymetrix, Inc

summary:
Identify and categorize copy number variation in normal populations
Keywords: Copy number variation detection

overall_design: 270 Hapmap samples were hybridized to 500K mapping arrays (Nsp and Sty) to identify variable copy number regions in the genome. NA15510 and NA10851 were hybridized to 500K mapping arrays in triplicate for parameter-tuning and validation of algorithm.


title: Bisphosphonate related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in MM

status: Public on Sep 25 2008

city: salamanca

first: Maria

middle: Eugenia

last: Sarasquete

state: salamanca

address: Paseo San Vicente 58-182

department: Hematology

country: Spain

institute: Hospital Universitario de Salamanca

summary: We have explored the potential role of genetics in the development of osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients under bisphosphonate therapy. A genome wide association study was performed using 500.568 single nucleotide polymorphisms (SNPs) in two series of homogeneously treated MM patients: one with ONJ (22 MM cases) and another without ONJ (65 matched MM controls). Four SNPs (rs1934951, rs1934980, rs1341162 and rs17110453) mapped within the Cytochrome P450-2C gene (CYP2C8) showed a different distribution between cases and controls with statistically significant differences (p=1.07x10-6, p=4.231x10-6, p=6.22x10-6 and p=2.15x10-5, respectively). SNP rs1934951 was significantly associated with a higher risk of ONJ development even after Bonferroni correction (P corrected value=0.02). Genotyping results displayed an overrepresentation of the T allele in cases as compared with controls (48% vs. 12%). Thus, individuals homozygous for the T allele had an increased likelihood of developing ONJ (Odds ratio 12.75, 95% confidence interval 3.7 to 43.5).

overall_design:
We studied 22 cases (MM with ONJ) and 65 controls (MM without ONJ), matched for age, gender and ethnicity (note: all of the cases and controls are Caucasian). All patients were enrolled in the GEM-00 protocol, which consists on polychemotherapy and autologous transplantation. All received BPs therapy, either Pamidronate (16 cases, 57 controls) or Zoledronic Acid (6 cases, 8 controls) planned for 2 years (median 22 months, range 9-24 months). Clinical characteristics were similar between controls and cases. Study protocols were approved by the ethics committee and written informed consent was obtained from all participants.
Each patient was genotyped using the Affymetrix GeneChip Mapping 500K set of microarrays (Affymetrix, Santa Clara, CA) according to the manufacturer’s recommendations. Genotypes were determined using the BRLMM algorithm with cases and controls undergoing joint cluster analysis, after ensuring a robust association test through quality filtering tests. Based on stringent quality control criteria a total of 339.972 SNPs were selected for subsequent analyses. Criteria for exclusion were: 1) call rate<90%, 2) minor allele frequency <5% and 3) deviations from Hardy-Weinberg equilibrium with a p<0.00001. Sexual chromosomes were excluded for analysis.
To test for allelic associations between SNPs and ONJ, we constructed 2x2 contingency tables and compared using the two-sided Fisher’s exact or Chisquare tests through SPSS software (SPSS 14.0, Inc. Chicago, IL, USA). P-values were corrected (Pc) using the Bonferroni correction. The strength of association was estimated by the odds ratio (OR), and their 95% confidence intervals (CI) were calculated by Cornfield methods. Linkage disequilibrium between SNPs was analyzed using the Arlequin Software (http://anthro.unige.ch/arlequin).

middle: E

first: Ramon

last: Garcia-Sanz

first: Luis

last: Marin

first: Miguel

last: Alcoceba

last: Chillon

first: Ana

last: Balanzategui

first: Carlos

last: Santamaria

first: Laura

last: Rosiñol

first: Javier

last: de la Rubia

last: Hernandez

first: Inmaculada

last: Garcia-Navarro

first: Juan

last: Lahuerta

first: Marcos

last: Gonzalez

first: Jesus

middle: F

last: San Miguel


title: Structural Variation of Chromosomes in Autism Spectrum Disorder.

status: Public on Dec 20 2007

city: Toronto

first: Christian

middle: R.

last: Marshall

state: ON

address: 101 College St.

department: Genetics & Genome Biology

country: Canada

institute: The Hospital for Sick Children

summary:
Chromosomal abnormalities have been identified in some individuals with Autism Spectrum Disorder (ASD), but their full etiologic role is unknown. Submicroscopic copy number variation (CNV) represents a considerable source of genetic variation in the human genome that contributes to phenotypic differences and disease susceptibility.
To explore the contribution CNV imbalances in ASD, we genotyped unrelated ASD index cases using the Affymetrix GeneChip® 500K single nucleotide polymorphism (SNP) mapping array.
Keywords: Whole Genome Mapping SNP Genotyping Array

overall_design: DNA derived from blood or lymphopblasts was hybridized to Affymetrix GeneChip® 500K mapping arrays. In total, 426 unrelated probands were analyzed along with 232 parents (116 trios). NspI and StyI arrays were analyzed for CNV using a combination of DNA Chip Analyzer (dChip), Copy Number Analysis for GeneChip (CNAG), and Genotyping Microarray based CNV Analysis (GEMCA).

first: Stephen

last: Scherer


title: SNP chip data of MCL

status: Public on Nov 13 2009

city: Tokyo

first: Motohiro

last: Kato

address: 7-3-1, Hongo, Bunkyo-ku

institute: University of Tokyo

summary:
Mantle cell lymphoma (MCL) is a lymphoma characterized by aberrant activation of CCND1/cyclin D1 followed by sequential genetic abnormalities. Genomic abnormalities in MCL have been extensively examined by classical cytogenetics and microarray-based comparative genomic hybridization techniques, pointing out a number of alterations in genomic regions that correlate with the neoplastic phenotype and survival. Recently, single nucleotide polymorphism genomic microarrays (SNP-chip) have been developed and used for analysis of cancer genomics. This technique allows detection of genomic changes with higher resolution, including loss of heterozygosity without changes of gene dosage, so-called acquired uniparental disomy (aUPD). As a result of the analysis, known alterations were confirmed by SNP arrays, including deletion of INK4A/ARF, duplication/amplification of MYC, deletion of ATM, and deletion of TP53. We also identified a duplication/amplification that occurred at 13q involving oncogenic microRNA, miR17-92. We found other genomic abnormalities, including duplication/amplification of cyclin D1, del(1p), del(6q), dup(3q) and dup(18q). Our SNP-chip analysis detected these abnormalities at high resolution, allowing us to narrow the size of the commonly deleted regions, including 1p and 6q. Our SNP-chip analysis detected a number of aUPD sites, including whole chromosome 9 aUPD and 9p aUPD. We also found an MCL case with 19p, leading to homozygous deletion of TNFSF genes.

keyword: SNP-chip; Kawmata_MCL

overall_design: To identify oncogenic lesions in mantle cell lymphoma (MCL), we performed a genome-wide analysis of primary MCL samples using high-density SNP arrays (Affymetrix GeneChip).

first: Norihiko

last: Kawamata

first: Seishi

last: Ogawa

first: Saskia

last: Gueller

first: Samuel

middle: H

last: Ross

first: Thien

last: Huynh

first: John

last: Chen

first: Andrew

last: Chang

first: Shayan

last: Nabavi-Nouis

first: Nairi

last: Megrabian

first: Reiner

last: Siebert

first: Jose

last: Martinez-Climentd

first: H

middle: P

last: Koeffler