Comparative genomic hybridization of 84 head and neck squamous cell carcinoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
DISEASE(S): head and neck squamous cell carcinoma
SUBMITTER: Aurelien de Reynies
PROVIDER: E-TABM-995 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:A Cartes dM-^RIdentite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net) | IntegraChipTM BAC pangenomic arrays (IntegraGen, Evry, France) : 59 ACTs samples including adrenocortical carcinomas (n=21) and adenomas (n=38) | Submitter : Olivia Barreau <olivia.barreau@inserm.fr> | Project leader : Jerome Bertherat <jerome.bertherat@inserm.fr>.
2011-04-18 | E-MTAB-659 | biostudies-arrayexpress
Project description:Purpose: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated mortality worldwide. Although the molecular mechanisms underpinning HCC are unknown, gene copy number and associated mRNA expression changes are frequently reported. Experimental Design: Comparative genomic hybridization arrays spotted with 4,041 bacterial artificial chromosome clones were used to assess copy number changes in 45 HCC tissues to identify chromosomal regions associated with the pathogenesis of HCC. Seventy more HCC tissues were used to validate candidate genes by using western blots and immunohistochemistry. Results: A total of 259 clones were associated with copy number changes that significantly differed between normal liver and HCC samples. The chromosomal region 1q32.1 containing the nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) gene was associated with tumor vascular invasion. Western blot analysis demonstrated that NUCKS1 was up-regulated in 37 of 70 (52.8%) HCC tissues compared with adjacent non-tumor tissues, and over-expressed in a vast majority of HCCs (44/52, 84.6%) as determined by immunohistochemical staining. Furthermore, immunostaining of both NUCKS1 and glypican-3 improved the diagnostic prediction of HCC. Knock-down of NUCKS1 by siRNA decreased the cell viability of the Hep3B cell line and reduced tumor formation in a xenograft mouse model. Functional enrichment analysis revealed the association of NUCKS1 with signal transduction, immunity and defense, and nucleotide metabolism pathways. Conclusions: NUCKS1 was identified as a potential oncogene at chromosomal 1q32.1 in patients with HCC, and it might be a valuable immunodiagnostic marker for HCC. Comparative genomic hybridization arrays spotted with 4,041 bacterial artificial chromosome clones were used to assess copy number changes in 45 HCC tissues and 25 normal liver tissues to identify chromosomal regions associated with the pathogenesis of HCC
2015-01-24 | E-GEOD-65237 | biostudies-arrayexpress
Project description:Myelodysplastic syndromes (MDS) are a group of clonal disorders of hematopoietic stem cells. Mesenchymal stem cells (MSC) are the progenitors of the Bone Marrow (BM) stroma and have been involved in the physiopathology of MDS. The presence of cytogenetic aberrations on MSC from MDS patients is controversial. The aim of the study is to characterize BM derived MSC from patients with MDS using: kinetic studies, immunophenotyping, fluorescent in situ hybridisation (FISH) analysis and genetic changes by array based comparative genomic hybridization (array-CGH). 32 cases of untreated MDS were included in the study. MSC from MDS achieved confluence at a slower rate than donor-MSC, and the antigenic expression of CD105 and CD104 was also lower. Array-CGH studies showed DNA genomic changes that were proved not to be somatic, and gains were more frequent than looses. The results of array-CGH were confirmed by FISH. When an unsupervised hierarchical cluster analysis was performed two clusters were identified: one of them included the 5q- syndrome patients, while the other incorporated the rest of the MDS patients. Our results shows, for the first time, that MSC from MDS display genomic aberrations, assessed by array-CGH and FISH, some of them specially linked to particular MDS subtypes. Keywords: Genomic comparison between mesenchymal cells 32 BM cells from âde novoâ MDS, corresponding to 29 patients, were included in the study. Male/female ratio was 14/15 and median age was 70 years (range 34-89). MDS diagnosis was established by peripheral blood counts and morphology, BM morphology and cytogenetic analyses and classified according to the WHO proposals. 12 Patientsâ characteristics are summarized in table 1. Three patients were included twice in the study: at the diagnosis of one RA (case 2) and two Unclassifiable MDS (cases 29,30), and at the progression into RAEB-2 (cases 16, 20 and 18). None of them had received treatment during this period of time, other than supportive therapy. Normal BM samples were obtained from 15 healthy donors, 8 males and 7 females, with a median age of 57 (range 37-88). Written informed consent was obtained from all patients and donors according to ethical guidelines of our institution. Genomic-wide analysis of DNA copy number changes of MSC from 13 cases was performed using array-CGH. Slides containing 3032 BACs were produced in âCentro de Investigación del Cáncerâ (Salamanca, Spain). The particular BAC and P-1 derived artificial chromosome set used to produce this array is distributed to academic institutions by the Welcome Trust Sanger Institute (Cambridge, United Kingdom) and contains targets spaced at ï» 1 Mb density over full genome, a set of subtelomeric sequences for each chromosome arm, and a few hundred probes selected for their involvement in oncogenesis. The clone content is available in the âCytoviewâ windows of the Sanger Institute mapping database site, Ensembl (http://www.ensembl.org/). According to this database, clones were ordered along the chromosomes. These clones were isolated from their bacterial cultures with the relevant antibiotics and the DNA was extracted with standard protocol Welcome Trust Sanger Institute (Cambridge, UK). 10 ng of DNA (BAC/PAC) was used as a template for three DOP-PC. 22;23 These products were ethanol precipitated and dissolved in distilled water. A minimum of three replicates per clone were printed by Microgrid II (Biorobotics) on each slide (Ultragaps Coated Slides, Corning) using the aqueous dimethylsulfoxide buffer as spotting solution. Briefly, for labelling reactions, 1 μg of nonamplified genomic DNA, test and reference were digested separately with DpnII restriction enzyme (New England Biolabs, Beverly, MA). For microarray hybridization, the digested DNAs were separately labelled using random primers (Bioprimer labelling kit, Invitrogen) and cyanine dye-3-dCTP and cyanine dye-5-dCTP fluorescent dye to paired hybridisation samples (Amersham Biosciences). The incorporated of the label nucleotide was quantified using the Nanodrop spectrophotometer. Labelled test and reference DNAs were mixed equitably, co-precipitated in presence of Cot-1 human DNA (Roche, Indianapolis, IN) with ethanol, washed, and resuspended in hybridization solution (50% Formamide, 10% Dextran sulfate, 2X standard saline citrate, 10 mM Tris pH 7.6, 2.7% sodium dodecyl sulfate and 10 μg/ μl of yeast tRNA). DNA mixtures were hybridized to the arrays in the TECAN HS4800 Pro according to the manufacturerâs recommended protocol. Images and signal intensities were acquired using GenePix4000B (Axon Instruments, Burlingame, CA) dual laser scanner in combination with GenePixPro4.0 (Axon Instruments) imaging software. Image and Data analysis. Spot intensities measured by the GenePix Pro 4.1 software (Axon Instruments, Wetsbur BV, Leuden, The Netherland). Pixel intensities for each feature were integrated and median values were determined, and the local background was calculated. For each spot the intensities were corrected by subtracting the local background for both wavelengths, and only spots with signal intensities al least threefold above background signal intensities were included in the analysis. The median of the ratios of all spots was calculated and used to normalize all data points. From each feature, the log2 value of the average of the normalization ratios of the spots was calculated and used to display the data. In addition, fluorescence ratios were normalized for each microarray using the print-tip loess method and the background subtraction with the Diagnosis and Normalization Arrays Data tool. 24 The cut-off level was determined for each individual experiment after avering the ratios from the two color-swith hybridizations and subsequent for normalization, and calculate the mean and Standard derivations to define the cut-off level as means plus/minus two times the standard derivations. The clones that showed possible changes were submitted to the Database of Genomics Variants (http://projects.tcag.ca/variation/) and chromosomal Imbalances and Phenotype in Humans using Ensembl Resources (DECIPCHER: http: www sanger. ac.uk /PostGenomics/decipher/. Clustering Unsupervised clustering We converted the relative ratio value for each BAC clones in each sample to score of 1 (gain/amplified), 0 (no change), or -1 (loss) based on the 2 SD standards described above and analyzed with Cluster and TreeView) 25 (Cluster and TreeView software) based on the average linkage method with the centered correlation metric was used (or Pearson Uncentered). Supervised Sam analysis was used http://www-stat.stanford.edu/ tibs/SAM) 26 to identify BACs that segregate subgroups on MSC. BACs with an SD of zero across the data set before analysis were removed.
2010-05-25 | E-GEOD-10822 | biostudies-arrayexpress
Project description:We genetically characterized parathyroid adenomas with large glandular weights, for which independent observations suggest pronounced clinical manifestations. Large parathyroid adenomas (LPTAs) were defined as the 5% largest sporadic parathyroid adenomas identified among the 590 cases operated on in our institution during 2005-2009. The LPTA group showed a higher relative number of male cases and significantly higher levels of total plasma and ionized serum calcium (P <0.001). Further analysis of 21 LPTAs revealed low MIB-1 proliferation index (0.1-1.5%), MEN1 mutations in 5 cases and one HRPT2 mutation. Total or partial loss of parafibromin expression was observed in 10 tumors, two of which also showed loss of APC expression. Using array-CGH, we demonstrated recurrent copy number alterations most frequently involving loss in 1p (29%), gain in 5 (38%) and loss in 11q (33%). Totally 21 minimal overlapping regions were defined for losses in 1p, 7q, 9p, 11 and 15q, and gains in 3q, 5, 7p, 8p, 16q, 17p and 19q. In addition, 12 tumors showed gross alterations of entire or almost entire chromosomes, most frequently gain of 5 and loss of 11. While gain of 5 was the most frequent alteration observed in LPTAs, it was only detected in a small proportion (4/58 cases, 7%) of parathyroid adenomas. A significant positive correlation was observed between parathyroid hormone level and total copy number gain (r = 0.48, P = 0.031). These results support that LPTAs represent a group of patients with pronounced parathyroid hyperfunction and associated with specific genomic features. We applied high-resolution array-CGH to assess copy number alterations (CNAs) in 21 tumors representing the 5% largest sporadic parathyroid adenomas in our institution.
2012-05-08 | E-GEOD-36511 | biostudies-arrayexpress
Project description:We analyzed ten adenoid cystic carcinomas of head and neck by array-based comparative genomic hybridization (a-CGH) using DNA chips spotted 4,030 BAC clones. After data smoothing by the adaptive weights smoothing (AWS) procedure with the gain and loss analysis of DNA (GLAD) algorithm, a total of 89 DNA copy number aberrations (DSCNAs) were detected. The frequent (≥30%) DSCNAs were loss of 6q24, 6q25, 8p23, 6q25, and 6q23 and gains of 6q23, 8p23, 9p11-13, and 22q13. High-level gain was detected on 12q12-15 including MDM2 in two cases. These two cases showed immunohistochemically positive status of MDM2 and negative status of p53 and p21. Furthermore, the total number of DSCNAs was significantly greater in ACC with loss of 6q than in other ACC, in ACC without loss of 8p23 than in other ACC, and in ACC with 8p23 gain than in ACC with 8p23 loss, respectively. Though there is a limit in the evidence, a-CGH detected several candidate chromosomal imbalances associated with DSCNA accumulation in ACC. 6q loss, 12q gain aCGH DNA copy number aberrations screening in human cancer adenoid cystic carcinoma (ACC).
2011-08-31 | E-GEOD-22328 | biostudies-arrayexpress
Project description:We analyzed specific genes for DNA copy number variation in hepatoma cells and investigated whether these factors are related to liver cancer phenotype. Chromosome 20p, which includes the ligand for Notch pathways, Jagged1, was found to be amplified in several types of hepatoma cells. In conclusion, amplification of Jagged1 contributed to mRNA expression that activates the Jagged1-Notch signaling pathway in liver cancer and led to poor outcome. Comparative genomic hybridization arrays spotted with 1,440 bacterial artificial chromosome clones were used to assess copy number changes in 7 hepatoma cell lines and 2 non-hepatoma cell lines to identify chromosomal regions associated with the pathogenesis of liver cancer.
2016-02-04 | E-GEOD-77224 | biostudies-arrayexpress
Project description:Thymic epithelial tumors are a group of neoplasms with heterogeneous histological features and clinical behavior. The identification of markers useful to predict patient prognosis and molecular targets for therapies is limited by a very little understanding of the biology of these neoplasms. We evaluated the copy number (CN) aberrations of genes involved in normal thymus development in thymic epithelial tumors, following the intriguing idea that the ectopic deregulation of genes relevant for proliferation and differentiation of embryonic cells, can contribute to tumor growth. Frequent CN losses of FOXC1 were observed in more aggressive tumors and correlated with a reduced protein expression; tumors negative for FOXC1 expression were associated with a shorter time to progression. In addition, FOXC1 showed tumor suppressor activity in in-vitro models. Our data indicate that FOXC1 loss can identify a group of thymic epithelial tumors with poor prognosis, possibly because its tumor suppressor properties. Two color array CGH of a series of 59 thymic epithelial tumors plus evaluation of 2 thymic carcinoma cell lines and one thymoma B1 cell line.
2013-05-03 | E-GEOD-23540 | biostudies-arrayexpress
Project description:Osteosarcomas are the most common primary malignant tumours of bone, and almost all conventional osteosarcomas are high-grade tumours showing complex genomic aberrations. We have integrated genome-wide genetic and epigenetic profiles from the EuroBoNeT panel of 19 human osteosarcoma cell lines based on microarray technologies. The cell lines showed complex patterns of DNA copy number changes, where copy number gains were significantly associated with gene-rich regions of the genome and losses with gene-poor areas. Integration of the datasets showed that the mRNA levels were regulated by either alterations in DNA copy number or DNA methylation. Using a recurrence threshold of 6/19 (> 30 %) cell lines, 348 genes were identified as having alterations of two data types (gain or hypo-methylation/over-expression, loss or hyper-methylation/under-expression). These genes are involved in embryonic skeletal system development and morphogenesis, as well as remodelling of extracellular matrix. Several genes were hyper-methylated and under-expressed compared to normal osteoblasts, and expression could be reactivated by demethylation using 5-Aza-2M-bM-^@M-^Y-deoxycytidine treatment for all four genes tested. Globally, there was as expected a significant positive association between gain and over-expression, loss and under-expression as well as hyper-methylation and under-expression, but gain was also associated with hyper-methylation and under-expression, suggesting that hyper-methylation may oppose the effects of increased copy number for some genes. Integrative analysis of genome-wide genetic and epigenetic alterations identified mechanistic dependencies and relationships between DNA copy number and DNA methylation in terms of regulating mRNA expression levels in osteosarcomas, contributing to better understanding of osteosarcoma biology. Comparison of DNA copy number changes in 19 osteosarcoma cell lines
2012-12-06 | E-GEOD-36003 | biostudies-arrayexpress
Project description:Pancreatic cancer is the fourth leading cancer-related death in United States. The clinical relevance of genomic imbalances in pancreatic cancer is uncertain. We performed array-comparative genomic hybridization (aCGH) in 44 resected pancreatic cancer specimens from a Korean cohort. We observed recurrent copy number gains were observed in chromosome 1q, 11q, 18q11.1-11.2, and 20q13.13; and losses in chromosome 2p, 9p, 10q, 14q, 15q, 18q12.2-23, 19q, 20q11.1, 21p, and 22q. High copy number gains, with log2 ratio >2.0, were observed in 4 cytobands, encoding genes such as G protein-coupled receptor 48, c-myc and gamma-catenin. By comparing the aCGH results of long survivors and short survivors, determined according to the median survival, we observed that loss of cytoband 18q22.3, encoding 5 genes, was the only alteration with significantly different frequencies. The copy number of the CPGL (Carboxypeptidase of glutamate-like) gene in cytoband 18q22.3 was found to be significantly associated with overall survival in univariate analyses (p=0.019 by log-rank test). This was subsequently assessed in the Italian cohort: 41 out of the 61 specimens carried deletion of the CPGL gene. Patients with deletion of the CPGL gene also had shorter overall survival (p=0.003 by log-rank test). Multivariate analysis of the two cohorts combined showed that loss of 18q22.3 / deletion of the CPGL gene was an independent poor prognostic factor for overall survival after adjusting for other factors which were found to impact the outcome (hazard ratio 2.72, p=0.0007). overexpression of the CPGL or its alternating splicing isoform CPGL-B in a pancreatic cancer cell lines resulted in slower proliferation of cells, G1 cell cycle arrest, and reduced migration activity. In conclusion, through aCGH analysis, we identified loss of 18q22.3 / deletion of the CPGL gene as potentially being an independent poor prognostic factor in resected pancreatic cancer. We further identified the CPGL gene as a potential tumor suppressor for pancreatic cancer cell lines. Array-comparative genomic hybridization was performed in 44 resected pancreatic cancer specimen from a Korean cohort. Genomic alteration relating to prognosis of the Korean cohort was further validated in a Italian cohort containing 61 resected pancreatic cancer specimens.
2011-04-21 | E-GEOD-28732 | biostudies-arrayexpress
Project description:Our study presents the first genetic models of de novo high-grade serous carcinomas (HGSC) that originate in fallopian tube secretory epithelial cells and recapitulate the key genetic alterations and precursor lesions characteristic of human invasive ovarian cancer. Genomic copy number analysis, using array CGH, was performed on murine tumors in order to compare the overlap of copy number alterations between HGSC models and TCGA data. Array CGH was performed on genomic DNA isolated from murine HGSC tumors. Genomic DNA from three normal mouse fallopian tubes was pooled and used as the reference.
2013-12-17 | E-GEOD-49827 | biostudies-arrayexpress