Genome-wide SNP Profiling of 27 Neuroblastoma Cell Lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE89968 | GEO | 2017/02/07
SECONDARY ACCESSION(S): PRJNA354536
REPOSITORIES: GEO
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Project description:Neuroblastoma cell lines are an important and cost-effective model used to study oncogenic drivers of the disease. While many of these cell lines have been previously characterized with SNP, methylation, and/or expression microarrays, there has not been an effort to comprehensively sequence these cell lines. Here, we present raw whole transcriptome data generated by RNA sequencing of 39 commonly-used neuroblastoma cell lines. This data can be used to perform differential expression analysis based on a genetic aberration or phenotype in neuroblastoma (eg: MYCN amplification status, ALK mutation status, 11q status, sensitivity to pharmacological pertubation). Additionally, we designed this experiment to enable structural variant and/or long-noncoding RNA analysis across these cell lines. Finally, as more DNase/ATAC and histone/transcription factor ChIP sequencing is performed in these cell lines, our RNA-Seq data will be an important complement to inform transcriptional targets as well as regulatory (enhancer or repressor) elements in neuroblastoma.
2017-02-07 | GSE89413 | GEO
Project description:TERT promoter muatations occur frequently in tumors of various origin. We here accessed the frequency of TERT pomoter mutations in 131 human primary neuroblastomas and 20 human neuroblastoma cell lines. No TERT promoter mutations were found in the 131 primary neuroblastomas. However, in the three cell lines SH-SY5Y, SH-EP and SK-N-SH a TERT promoter mutation was detected. Sanger sequencing indicated a homozygous mutation. To confirm loss of heterozygosity (LOH) we performed Affymetrix CytoScanHD SNP arrays. Indeed LOH could be confirmed.
2015-03-03 | GSE66422 | GEO
Project description:TERT promoter muatations occur frequently in tumors of various origin. We here accessed the frequency of TERT pomoter mutations in 131 human primary neuroblastomas and 20 human neuroblastoma cell lines. No TERT promoter mutations were found in the 131 primary neuroblastomas. However, in the three cell lines SH-SY5Y, SH-EP and SK-N-SH a TERT promoter mutation was detected. Sanger sequencing indicated a homozygous mutation. To confirm loss of heterozygosity (LOH) we performed Affymetrix CytoScanHD SNP arrays. Indeed LOH could be confirmed. SNP arry experiments were performed according to the standard protocol for Affymetrix CytoScanHD arrays (Affymetrix, Santa Clara). Briefly, a 250 ng sample of genomic DNA was digested with NspI, ligated to adaptors, amplified by PCR, fragmented and biotin-labeled. The labeled samples were hybridized to Affymetrix CytoscanHD arrays, followed by washing, staining and scanning in the Affymetrix GeneChip Scanner 3000. Analysis was performed using the Affymetrix Chromosome Analysis Suite v2.1.
2015-03-03 | E-GEOD-66422 | biostudies-arrayexpress
Project description:Stromal contamination is one of the major confounding factors in the analysis of primary solid tumor samples by single nucleotide polymorphism (SNP) arrays. As we propose to employ genome-wide SNP microarray analysis as a diagnostic platform for neuroblastoma, the sensitivity, specificity, and accuracy of these studies must be optimized. In order to investigate the effects of stroma, we derived early passage cell lines from nine primary tumors and compared their genomic signature with that of the primary tumors by 100K SNP array analysis. The average concordance between tumor and cell line for raw LOH (loss of heterozygosity) calls was 96% (range 91%-99%) and for raw copy number alterations (CNA), 71% (range 43%-87%). In general, there were a larger number of LOH events identified in the cell lines compared to the matched tumor samples (mean increase 3.2% ± 1.9%). We have developed an algorithm that shows that the presence of stroma contributes to under-reporting of LOH and copy number loss (CNL). Notable findings in this sample set were uniparental disomy (UPD) of chromosome arms 11p, 1q, 14q, and 15q and a novel area of amplification on chromosome band 11p15. Our analysis demonstrates that LOH was identified significantly more often in derived cell lines compared to the original tumor samples. While these may in part be due to clonal selection during adaptation to tissue culture, our study indicates contamination by normal stromal elements may be a major contributing factor in underestimation of LOH and CNL events. Keywords: genome wide SNP analysis Nine human neuroblastoma tumor samples with paired blood samples and derivative cell lines
2009-01-31 | E-GEOD-14656 | biostudies-arrayexpress
Project description:Stromal contamination is one of the major confounding factors in the analysis of primary solid tumor samples by single nucleotide polymorphism (SNP) arrays. As we propose to employ genome-wide SNP microarray analysis as a diagnostic platform for neuroblastoma, the sensitivity, specificity, and accuracy of these studies must be optimized. In order to investigate the effects of stroma, we derived early passage cell lines from nine primary tumors and compared their genomic signature with that of the primary tumors by 100K SNP array analysis. The average concordance between tumor and cell line for raw LOH (loss of heterozygosity) calls was 96% (range 91%-99%) and for raw copy number alterations (CNA), 71% (range 43%-87%). In general, there were a larger number of LOH events identified in the cell lines compared to the matched tumor samples (mean increase 3.2% ± 1.9%). We have developed an algorithm that shows that the presence of stroma contributes to under-reporting of LOH and copy number loss (CNL). Notable findings in this sample set were uniparental disomy (UPD) of chromosome arms 11p, 1q, 14q, and 15q and a novel area of amplification on chromosome band 11p15. Our analysis demonstrates that LOH was identified significantly more often in derived cell lines compared to the original tumor samples. While these may in part be due to clonal selection during adaptation to tissue culture, our study indicates contamination by normal stromal elements may be a major contributing factor in underestimation of LOH and CNL events. Keywords: genome wide SNP analysis
2009-01-31 | GSE14656 | GEO
Project description:we used single-cell transcriptomics and genotyping arrays to characterize 17 neuroblastoma samples across different risk groups and genetic subsets.Fresh samples, obtained from surgical resections and core biopsies, were used for genome variation profiling. DNA extraction from neuroblastoma samples was performed using the DNeasy blood and tissue kit (Qiagen) according to the manufacturer’s protocol. DNA quality was assessed using the Tapestation platform (Agilent). SNP microarray analysis was performed using the Cytoscan HD Array (Affymetrix) and data was processed using the Chromosome Analysis Suite version 3.3.0.139.
2022-12-14 | GSE147773 | GEO
Project description:Understanding the aberrant transcriptional landscape of neuroblastoma is necessary to provide insight to the underlying influences of the initiation, progression and persistence of this developmental cancer. Here, we present chromatin immunoprecipitation sequencing (ChIP-Seq) data for the oncogenic transcription factors, MYCN and MYC, as well as regulatory histone marks H3K4me1, H3K4me3, H3K27Ac, and H3K27me3 in ten commonly used human neuroblastoma-derived cell line models. In addition, for all of the profiled cell lines we provide ATAC-Seq as a measure of open chromatin. We validate specificity of global MYCN occupancy in MYCN amplified cell lines and functional redundancy of MYC occupancy in MYCN non-amplified cell lines. Finally, we show with H3K27Ac ChIP-Seq that these cell lines retain expression of key neuroblastoma super-enhancers (SE). We anticipate this dataset, coupled with available transcriptomic profiling on the same cell lines, will enable the discovery of novel gene regulatory mechanisms in neuroblastoma. This SuperSeries is composed of the SubSeries listed below.
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Project description:Purpose: Neuroblastoma is characterized by substantial clinical heterogeneity. Despite intensive treatment, the survival rates of high-risk neuroblastoma patients are still disappointingly low. Somatic chromosomal copy number aberrations have been shown to be associated with patient outcome, particularly in low- and intermediate-risk neuroblastoma patients. To improve outcome prediction in high-risk neuroblastoma, we aimed to design a prognostic classification method based on copy number aberrations. Methods: In an international collaboration, normalized high-resolution DNA copy number data (arrayCGH and SNP arrays) from 556 high-risk neuroblastomas obtained at diagnosis were collected from nine collaborative groups and segmented using the same method. We applied logistic and Cox proportional hazard regression to identify genomic aberrations associated with poor outcome. Results: In this study, we identified two types of copy number aberrations that are associated with extremely poor outcome. (i) Distal 6q losses were detected in 5.9% of patients and were associated with a ten-year survival probability of only 3.4%. (ii) Amplifications of regions not encompassing the MYCN locus were detected in 18% of patients and were associated with a ten-year survival probability of only 5.8%. Conclusion: Using a unique large copy number dataset of high-risk neuroblastoma cases, we identified a small subset of high-risk neuroblastoma patients with extremely low survival probability that might be eligible for inclusion in clinical trials of new therapeutics. The amplicons may also nominate alternative treatments that target the amplified genes.
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Project description:Ovarian development and maintenance are poorly understood, but diseases affecting them can offer insights into their underlying mechanisms. XX-female gonadal dysgenesis (XX-GD) is a rare, genetically heterogeneous disorder characterized by underdeveloped, dysfunctional ovaries with subsequent lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism. We used SNP arrays to perform homozygosity mapping in order to detect informative genomic regions which are homozygous and shared among affected individuals. This analysis identified genomic regions in which the mutated gene causing the XX-GD phenotype in the affected individuals may reside. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from peripheral blood samples.
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Project description:SNP arrays were used to derive copy number estimates and identify amplifications and deletions in melanomas These copy number breakpoints were compared to gene fusions identified by second generation sequencing of cDNA
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