SNP data from Neuroblastoma samples
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE12494 | GEO | 2008/10/10
SECONDARY ACCESSION(S): PRJNA112975
REPOSITORIES: GEO
Similar Datasets
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:Neuroblastoma (NBL) is an embryonal cancer of the sympathetic nervous system (SNS) that causes 15% of pediatric cancer deaths. High-risk neuroblastoma is characterized by N-Myc amplification and segmental chromosomal gains and losses. Due to limited disease models, the etiology of neuroblastoma is largely unknown, including both the cell of origin and the majority of oncogenic drivers. We have established a novel system for studying neuroblastoma based on the transformation of neural crest cells (NCCs), the progenitor cells of the SNS, isolated from mouse embryonic day 9.5 trunk neural tube explants. Based on pathology and gene expression analysis, we report the first successful transformation of wild-type NCCs into NBL by enforced expression of N-Myc to generate phenotypically and molecularly accurate tumors that closely model human MYCN-amplified NBL. Using comparative genomic hybridization, we found that NCC-derived neuroblastoma tumors acquired copy number gains and losses that are syntenic to those observed in human MYCN-amplified neuroblastoma including 17q gain, 2p gain and loss of 1p36. When p53-compromised NCCs were transformed with N-Myc we generated primitive neuroectodermal tumors with divergent differentiation including osteosarcoma. These subcutaneous tumors were metastatic to regional lymph nodes, liver and lung. Our novel experimental approach accurately models human neuroblastoma and establishes a new system with potential to study early stages of neuroblastoma oncogenesis, to functionally assess neuroblastoma oncogenic drivers, and to characterize neuroblastoma metastasis.
2017-09-25 | GSE94914 | 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: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:Chromosome 17q gain is an independent prognostic marker in neuroblastoma, harboring several potential oncogenes including IGF2BP1 and BIRC5. IGF2BP1 was shown to be upregulated in unfavorable neuroblastoma and correlates with poor patient survival. Here, we report that overexpression of IGF2BP1 in a transgenic mouse model induces neuroblastoma with all characteristics known for human neuroblastoma, including MYCN upregulation and genomic aberrations. Furthermore, we demonstrate that genes located at chromosome 17q have an exceptionally high potential as therapeutic targets in addition to a combined inhibition of IGF2BP1 and BIRC5 resulting in additive effects.
2023-05-31 | GSE221848 | GEO
Project description:Chromosome 17q gain is an independent prognostic marker in neuroblastoma, harboring several potential oncogenes including IGF2BP1 and BIRC5. IGF2BP1 was shown to be upregulated in unfavorable neuroblastoma and correlates with poor patient survival. Here, we report that overexpression of IGF2BP1 in a transgenic mouse model induces neuroblastoma with all characteristics known for human neuroblastoma, including MYCN upregulation and genomic aberrations. Furthermore, we demonstrate that genes located at chromosome 17q have an exceptionally high potential as therapeutic targets in addition to a combined inhibition of IGF2BP1 and BIRC5 resulting in additive effects.
2023-05-31 | GSE181581 | GEO
Project description:Chromosome 17q gain is an independent prognostic marker in neuroblastoma, harboring several potential oncogenes including IGF2BP1 and BIRC5. IGF2BP1 was shown to be upregulated in unfavorable neuroblastoma and correlates with poor patient survival. Here, we report that overexpression of IGF2BP1 in a transgenic mouse model induces neuroblastoma with all characteristics known for human neuroblastoma, including MYCN upregulation and genomic aberrations. Furthermore, we demonstrate that genes located at chromosome 17q have an exceptionally high potential as therapeutic targets in addition to a combined inhibition of IGF2BP1 and BIRC5 resulting in additive effects.
2023-05-31 | GSE181580 | GEO
Project description:Chromosome 17q gain is an independent prognostic marker in neuroblastoma, harboring several potential oncogenes including IGF2BP1 and BIRC5. IGF2BP1 was shown to be upregulated in unfavorable neuroblastoma and correlates with poor patient survival. Here, we report that overexpression of IGF2BP1 in a transgenic mouse model induces neuroblastoma with all characteristics known for human neuroblastoma, including MYCN upregulation and genomic aberrations. Furthermore, we demonstrate that genes located at chromosome 17q have an exceptionally high potential as therapeutic targets in addition to a combined inhibition of IGF2BP1 and BIRC5 resulting in additive effects.
2023-05-31 | GSE181579 | GEO
Project description:Chromosome 17q gain is an independent prognostic marker in neuroblastoma, harboring several potential oncogenes including IGF2BP1 and BIRC5. IGF2BP1 was shown to be upregulated in unfavorable neuroblastoma and correlates with poor patient survival. Here, we report that overexpression of IGF2BP1 in a transgenic mouse model induces neuroblastoma with all characteristics known for human neuroblastoma, including MYCN upregulation and genomic aberrations. Furthermore, we demonstrate that genes located at chromosome 17q have an exceptionally high potential as therapeutic targets in addition to a combined inhibition of IGF2BP1 and BIRC5 resulting in additive effects.
2023-05-31 | GSE181559 | GEO
Project description:Loss of heterozygosity (LOH) at 1p36 is a frequent chromosomal event in a broad range of human cancers with increased incidence observed in nervous system malignancies, including neuroblastoma (NBL). MYCN amplification and 1p36 deletions are highly correlated markers of tumor aggressiveness in NBL. While short distal 1p36 losses are associated with single copy MYCN tumors, larger hemizygous 1p deletions correlate with MYCN amplification, suggesting that two tumor suppressor regions exist in 1p36, a distal and proximal region, which have MYCN-independent and dependent roles. To interrogate this, we genome-edited a proximal candidate, Arid1a, a distal candidate, Chd5, and engineered a syntenic 1p36 LOH deletion in primary mouse NCCs, the likely cell of origin for NBL. Chd5 deletions were found to confer most of the pro-tumorigenic functions of 1p36 LOH in cells expressing endogenous Mycn levels. In contrast, reduced tumor latency in Mycn-driven oncogenesis significantly correlated with the loss of Arid1a. Gene expression analysis found that tumors presenting early onset display a Polycomb Repressive Complex 2 (PRC2) signature and an impaired Trp53 signaling pathway signature. Our findings delineate the tumor suppressor functions of 1p36 LOH in NBL and potentially provide critical insights for the constellation of cancers with 1p36 deletion.
2019-12-01 | GSE123281 | GEO