Affymetrix CytoScan HD data on neuroblastoma cell lines
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE209728 | GEO | 2022/11/10
REPOSITORIES: GEO
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Project description:Gene expression analysis was performed on 30 Neuroblastomas to identify genes whose transcription is significantly altered by recurrent chromosomal alterations. Genomic copy number losses and gains had been delineated in the tumours using FISH and SNP arrays. We have identified genes significantly altered by 7 recurrent alterations: 1p, 3p, 4p, 10q and 11q loss, 2p and 17q gain, and genes co-amplified and over-expressed as a result of MYCN amplification. Identifying genes whose expression is consistently altered by chromosomal gains or losses is an important step in defining genes of biological relevance in a wide variety of tumour types. However, additional criteria are needed to discriminate further among the large number of candidate genes identified. This is particularly true for neuroblastoma, where multiple genomic copy number changes of proven prognostic value exist. We have used Affymetrix microarrays and a combination of fluorescent in-situ hybridisation and single nucleotide polymorphism (SNP) microarrays to establish expression profiles and delineate copy number alterations in 30 primary neuroblastomas. Experiment Overall Design: 30 neuroblastomas were obtained from patients of all stages (10 patients - stage 1, 2, 3 or 4s disease, 20 patients - stage 4 disease). RNA samples were extracted and analysed using Affymetrix Human Genome U133 Plus 2.0 Arrays. Patient were treated according to the United Kingdom Childrenâs Cancer Study Group [UKCCSG], European Neuroblastoma Study Group and Localised Neuroblastoma European Study Group protocols.
2008-10-26 | E-GEOD-13136 | biostudies-arrayexpress
Project description:Gene expression analysis was performed on 30 Neuroblastomas to identify genes whose transcription is significantly altered by recurrent chromosomal alterations. Genomic copy number losses and gains had been delineated in the tumours using FISH and SNP arrays. We have identified genes significantly altered by 7 recurrent alterations: 1p, 3p, 4p, 10q and 11q loss, 2p and 17q gain, and genes co-amplified and over-expressed as a result of MYCN amplification. Identifying genes whose expression is consistently altered by chromosomal gains or losses is an important step in defining genes of biological relevance in a wide variety of tumour types. However, additional criteria are needed to discriminate further among the large number of candidate genes identified. This is particularly true for neuroblastoma, where multiple genomic copy number changes of proven prognostic value exist. We have used Affymetrix microarrays and a combination of fluorescent in-situ hybridisation and single nucleotide polymorphism (SNP) microarrays to establish expression profiles and delineate copy number alterations in 30 primary neuroblastomas. Keywords: Disease State Analysis
2008-10-09 | GSE13136 | GEO
Project description:Gene expression analysis was performed on 30 Neuroblastomas to identify genes whose transcription is significantly altered by recurrent chromosomal alterations. Genomic copy number losses and gains had been delineated in the tumours using FISH and SNP arrays. We have identified genes significantly altered by 7 recurrent alterations: 1p, 3p, 4p, 10q and 11q loss, 2p and 17q gain, and genes co-amplified and over-expressed as a result of MYCN amplification. Subsequently, correlation of microarray data with survival and expression within rodent neuroblastomas were used to identify genes likely to be involved in the disease progression, and identified a significant excess of differentially expressed genes which correlated with survival within the minimally altered regions on 17q and 4p; Identifying genes whose expression is consistently altered by chromosomal gains or losses is an important step in defining genes of biological relevance in a wide variety of tumour types. However, additional criteria are needed to discriminate further among the large number of candidate genes identified. This is particularly true for neuroblastoma, where multiple genomic copy number changes of proven prognostic value exist. We have used Affymetrix microarrays and a combination of fluorescent in-situ hybridisation and single nucleotide polymorphism (SNP) microarrays to establish expression profiles and delineate copy number alterations in 30 primary neuroblastomas. Correlation of microarray data with patient survival and analysis of expression within rodent neuroblastoma cell lines were then used to further define genes likely to be involved in the disease process. Using this approach we identify >1000 genes within 8 recurrent genomic alterations (loss of 1p, 3p, 4p, 10q and 11q, 2p gain, 17q gain, and the MYCN amplicon) whose expression is consistently altered by copy number change. Of these, 84 correlate with patient survival, with the minimal regions of 17q gain and 4p loss being significantly enriched for such genes. Orthologues of all but one of these genes on 17q are overexpressed in rodent neuroblastoma cell lines. A significant excess of SNPs whose copy number correlates with survival is also observed on proximal 4p in stage 4 tumours, and we find that deletion of 4p is associated with improved outcome in an extended cohort of tumours. These results define the major impact of genomic copy number alterations upon transcription within neuroblastoma, and highlight genes on distal 17q and proximal 4p for downstream analyses. They also suggest that integration of discriminators such as survival and comparative gene expression with microarray data may be useful in the identification of critical genes within regions of loss or gain in many human cancers. Experiment Overall Design: Chromosomal gains and losses were delineated in Stage 4 neuroblastomas to facilitate, in combination with expression array data, the identification of genes within regions of gain and loss whose expression is significantly altered by copy number change.
2008-10-26 | E-GEOD-13137 | biostudies-arrayexpress
Project description:Genomic profiles of tumor DNA obtained from biopsies were systematically compared to corresponding samples of circulating cell free tumor DNA. The aim was to investigate correspondance between numerical, segmental and focal aberrations, as well as precision in detection and resolution of oncoscan array performance on cfDNA.
2016-11-30 | GSE85937 | GEO
Project description:Gene expression analysis was performed on 30 Neuroblastomas to identify genes whose transcription is significantly altered by recurrent chromosomal alterations. Genomic copy number losses and gains had been delineated in the tumours using FISH and SNP arrays. We have identified genes significantly altered by 7 recurrent alterations: 1p, 3p, 4p, 10q and 11q loss, 2p and 17q gain, and genes co-amplified and over-expressed as a result of MYCN amplification. Subsequently, correlation of microarray data with survival and expression within rodent neuroblastomas were used to identify genes likely to be involved in the disease progression, and identified a significant excess of differentially expressed genes which correlated with survival within the minimally altered regions on 17q and 4p Identifying genes whose expression is consistently altered by chromosomal gains or losses is an important step in defining genes of biological relevance in a wide variety of tumour types. However, additional criteria are needed to discriminate further among the large number of candidate genes identified. This is particularly true for neuroblastoma, where multiple genomic copy number changes of proven prognostic value exist. We have used Affymetrix microarrays and a combination of fluorescent in-situ hybridisation and single nucleotide polymorphism (SNP) microarrays to establish expression profiles and delineate copy number alterations in 30 primary neuroblastomas. Correlation of microarray data with patient survival and analysis of expression within rodent neuroblastoma cell lines were then used to further define genes likely to be involved in the disease process. Using this approach we identify >1000 genes within 8 recurrent genomic alterations (loss of 1p, 3p, 4p, 10q and 11q, 2p gain, 17q gain, and the MYCN amplicon) whose expression is consistently altered by copy number change. Of these, 84 correlate with patient survival, with the minimal regions of 17q gain and 4p loss being significantly enriched for such genes. Orthologues of all but one of these genes on 17q are overexpressed in rodent neuroblastoma cell lines. A significant excess of SNPs whose copy number correlates with survival is also observed on proximal 4p in stage 4 tumours, and we find that deletion of 4p is associated with improved outcome in an extended cohort of tumours. These results define the major impact of genomic copy number alterations upon transcription within neuroblastoma, and highlight genes on distal 17q and proximal 4p for downstream analyses. They also suggest that integration of discriminators such as survival and comparative gene expression with microarray data may be useful in the identification of critical genes within regions of loss or gain in many human cancers. Keywords: Disease State Analysis
2008-10-09 | GSE13137 | GEO
Project description:Methylome of tumor cell-free DNA (cfDNA) has emerged as a powerful non-invasive technique for cancer subtyping and prognosis. However, its application is frequently hampered by the quality and total cfDNA yield. Here we demonstrate the feasibility of very low-input cfDNA for whole-methylome and copy-number profiling studies using enzymatic conversion of unmethylated cysteines (EMSEQ) to better preserve DNA integrity. We demonstrate that cfDNA methylation of our cohort was comparable with in situ cohorts and built a model that accurately predict MYCN amplification or 11q deletion in validation cohorts. RASSF1A methylation precedes this divergent methylome signature, supporting common and different epigenetic origins. After stratification by 11q, eight CpG methylations show additional prognostic value and two reveal known preclinical targets (CSF1R, CCR7). Methylation in CSF1R and CCR7 associated with differential expression levels and poorer prognosis. Noteworthy, haploinsufficiency of genes located on 11q that repair DNA double-strand breaks display reduced expression by a mechanism independent of promoter methylation. Conclusions: RASSF1A is an early hypermethylation defect that may predispose to later genetic and epigenetic alterations specific to MYCN-amplified or 11q-deleted high-risk neuroblastomas. CSF1R and CCR7 hypermethylation are a hallmark of high-risk 11q-deleted neuroblastomas that could be exploited therapeutically with immunomodulators to override immunosupression and relapse. Our novel findings provide support for use of liquid biopsy as an optimal strategy to assess methylomes of neuroblastoma patients for a precision medicine approach.
2023-01-25 | GSE221317 | GEO
Project description:Standard cytogenetic GTG-banding analysis (550 bands) revealed an interstitial deletion on 15q21q22 chromosomal region. Refinement of the 15q21.2 deletion intervals was conducted using aCGH (Cytoscan HD, Affymetrix) on DNA samples from the patient. This assay revealed the presence of submicroscopic alterations on chromosomes 1, 9 and 15. The result was arr[hg19] 9p24.1(6,619,823-6,749,335)x3, 1q44(248,688,586-248,795,277)x1, 15q21.2q22.2(50,848,301-61,298,006)x1. Affymetrix CytoScan HD arrays were performed according to the manufacturer's directions on DNA extracted from peripheral blood samples.
2014-06-21 | E-GEOD-58694 | biostudies-arrayexpress
Project description:Standard cytogenetic GTG-banding analysis (550 bands) revealed an interstitial deletion on 15q21q22 chromosomal region. Refinement of the 15q21.2 deletion intervals was conducted using aCGH (Cytoscan HD, Affymetrix) on DNA samples from the patient. This assay revealed the presence of submicroscopic alterations on chromosomes 1, 9 and 15. The result was arr[hg19] 9p24.1(6,619,823-6,749,335)x3, 1q44(248,688,586-248,795,277)x1, 15q21.2q22.2(50,848,301-61,298,006)x1.
2014-06-21 | GSE58694 | GEO
Project description:Autism spectrum disorder (ASD) is a complex heterogeneous developmental disease with a significant genetic background that is frequently caused by rare copy number variants (CNV). The aim of the study was to identify new candidate genes for ASD in the studied cohort of ASD-diagnosed patients. We used chromosomal microarray analysis (CMA) - a Cytoscan HD (Affymetrix, Santa Clara, CA, USA) to detect CNV in 87 ASD patients and their relatives and evaluated their clinical significance. Pathogenic and likely pathogenic mutations were identified by CMA in 8 and 9 ASD patients, respectively. CMA revealed 89 rare CNV: 8 pathogenic, 12 designated VOUS - likely pathogenic, 12 VOUS - uncertain, and 57 VOUS - likely benign or benign. CNV (pathogenic/VOUS-likely pathogenic/VOUS - uncertain) overlapping the same gene in more than one patient were observed in DOCK8 gene and PARK2 gene. This work presents new evidence about the possible roles of PARK2 and DOCK8 in the etiology of ASD, and suggests CTNNA2 as a candidate gene for ASD risk.
2018-05-25 | GSE114870 | GEO
Project description:Neuroblastoma is an often aggressive childhood cancer with several large chromosomal regions showing recurrent gains or losses. Chromosome 7q is gained in 40-60% of neuroblastomas, but despite being the second most frequent genomic aberration, no oncogenes have been linked to 7q gain.
2013-10-06 | GSE28409 | GEO