Neuroblastoma: MYCN normal vs. MYCN amplified
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Pei-Yi Wu
PROVIDER: E-GEOD-53371 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:To evaluate the expression of genes associated with MYCN in NB, 10 tumors with MYCN amplification and 10 with normal MYCN copy number were subjected to oligonucleotide microarray using Agilent oligo microarray chips.
2013-12-17 | GSE53371 | GEO
Project description:MYCN amplification (MNA) is a defining feature of high-risk neuroblastoma (NB) that predicts poor prognosis. However, whether genes within or in close proximity to the MYCN amplicon also contribute to aggressiveness in MNA+ NB remains poorly understood. Here we identify that GREB1, a transcription factor encoding gene neighboring the MYCN locus, is frequently co-expressed with MYCN, and promotes cell survival in MNA+ NB. GREB1 controls gene expression independently of MYCN in MNA+ NB, among which we uncover Myosin 1B (MYO1B) as being highly expressed in MNA+ NB. MYO1B promotes aggressive features, including invasive capacity in vitro, as well as extravasation and distant metastasis in vivo. Global secretome and proteome profiling further delineate MYO1B as a major regulator of secretome reprogramming in MNA+ NB cells. Moreover, we identify the cytokine MIF as an important pro-invasive and pro-metastatic mediator of MYO1B activity. Together, we have identified a putative GREB1-MYO1B-MIF axis as an unconventional mechanism that promotes the aggressiveness of MNA+ NB, and independently of MYCN. Furthermore, we find that MYO1B is upregulated in association with other oncoproteins during cellular transformation, and is dramatically increased in multiple human cancer types, suggesting a crucial role of MYO1B in cancers in addition to MNA+ NB.
2023-10-24 | PXD039410 | Pride
Project description:The ALK^F1174L mutation is associated with intrinsic and acquired resistance to crizotinib and cosegregates with MYCN in neuroblastoma. In this study, we generated a mouse model overexpressing ALK^F1174L in the neural crest. Comapred to mice expressing ALK^F1174L or MYCN alone, combined expression of the two aberrations led to development of neuroblastoma with a shorter latency and higher penetrance. Here, we evaluated the transcriptional profiles of MYCN-driven neuroblastomas with or without the expression of ALK^F1174L to determine the pathogenic consequences of the ALK^F1174L/MYCN interaction in neuroblastoma. 10 mice were analysed in this study. Five ALK^F1174L/MYCN tumors were compared with five MYCN tumors. Total RNA was extracted, samples were labeled and processed using the Agilent Low Input Quick Amp two color Cy3(sample) and Cy5 (mouse reference) labeling kit and hybridized to Agilent SurePrint G3 Mouse Gene Expression arrays.
2012-07-04 | E-GEOD-35560 | biostudies-arrayexpress
Project description:To identify the MYCN transcription factor binding sites across the genome, we performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) using anti-MYCN and anti-IgG antibodies on a MYCN-amplified NB cell line, SK-N-BE(2)-C. Identification of MYCN binding in neuroblastoma cells.
2016-05-16 | E-GEOD-72640 | biostudies-arrayexpress
Project description:Neuroblastoma, the most common extracranial pediatric solid tumor, is responsible for 15% of all childhood cancer deaths. Patients frequently present at diagnosis with metastatic disease, particularly to the bone marrow. Advances in therapy and understanding of the metastatic process have been limited due in part, to the lack of animal models harboring bone marrow disease. The widely employed transgenic model, the TH-MYCN mouse, exhibits limited metastasis to this site. Here we establish the first genetic immunocompetent mouse model for metastatic neuroblastoma with enhanced secondary tumors in the bone marrow. This model recapitulates two frequent alterations in metastatic neuroblasoma, over-expression of MYCN and loss of caspase-8 expression. In this model, the mouse caspase-8 gene was deleted in neural crest lineage cells by crossing a TH-Cre transgenic mouse with a caspase-8 conditional knockout mouse. This mouse was then crossed with the neuroblastoma prone TH-MYCN mouse. While over-expression of MYCN by itself rarely caused bone marrow metastasis (5% average incidence), combining MYCN overexpression and caspase-8 deletion significantly increased bone marrow metastasis (37% average incidence). Loss of caspase-8 expression did not alter the site, incidence, or latency of the primary tumors. However, secondary tumors were detected in the bone marrow of these mice as early as week 9-10. The mouse model described in this work is a valuable tool to enhance our understanding of metastatic neuroblastoma and treatment options and underscores the role of caspase-8 in neuroblastoma progression. Survey of spontateous 13 NB tumors in wt and transgenic mice
2013-05-22 | E-GEOD-42254 | biostudies-arrayexpress
Project description:Purpose: Clinical courses of neuroblastomas (NBs) range from rapid progression with fatal outcome despite intensive multimodality therapies to spontaneous regression. Amplified MYCN oncogene defines a subgroup with poor outcome. However, a substantial number of MYCN single-copy NBs exhibits an aggressive phenotype similar to that of MYCN-amplified NBs even in the absence of high MYCN mRNA and/or protein levels. Experimental Design: To identify shared molecular mechanisms that mediate the aggressive phenotype in MYCN amplified and single-copy high-risk NBs, we defined genetic programs evoked by ectopically expressed MYCN in vitro and analyzed them in high-risk versus low-risk NB tumors (n=49) using cDNA microarrays. Candidate gene and protein expression was validated in a separate cohort of 117 patients using quantitative PCR (QPCR) and in a panel of NB tumors using immunohistochemistry. Results: We identified a genetic signature characterized by Skp2, encoding the F-box protein of the SCFSkp2 E3-ligase, and a subset of MYCN and of E2F targets to be highly expressed in high-risk NBs. We validated the findings for Skp2 and analyzed its expression in relation to MYCN and E2F-1 expression in a separate cohort (n=117) using QPCR. Most importantly, high Skp2 expression proved to be a highly significant marker of dire prognosis independent of both MYCN status and disease stage, on the basis of multivariate analysis of event-free survival (hazard ratio, 3.54
2007-06-01 | E-CVDE-2 | biostudies-arrayexpress
Project description:The MYCN locus is amplified in about half of high-risk neuroblastoma tumors. To identify genomic loci occupied by MYCN protein in the MYCN-amplified neuroblastoma cell lines NGP, Kelly and NB-1643, we performed chromatin immunoprecipitation coupled with Next-Generation Sequencing (ChIP-seq) using an anti-MYCN antibody.
2017-08-02 | GSE94782 | GEO
Project description:Purpose: Clinical courses of neuroblastomas (NBs) range from rapid progression with fatal outcome despite intensive multimodality therapies to spontaneous regression. Amplified MYCN oncogene defines a subgroup with poor outcome. However, a substantial number of MYCN single-copy NBs exhibits an aggressive phenotype similar to that of MYCN-amplified NBs even in the absence of high MYCN mRNA and/or protein levels. Experimental Design: To identify shared molecular mechanisms that mediate the aggressive phenotype in MYCN amplified and single-copy high-risk NBs, we defined genetic programs evoked by ectopically expressed MYCN in vitro and analyzed them in high-risk versus low-risk NB tumors (n=49) using cDNA microarrays. Candidate gene and protein expression was validated in a separate cohort of 117 patients using quantitative PCR (QPCR) and in a panel of NB tumors using immunohistochemistry. Results: We identified a genetic signature characterized by Skp2, encoding the F-box protein of the SCFSkp2 E3-ligase, and a subset of MYCN and of E2F targets to be highly expressed in high-risk NBs. We validated the findings for Skp2 and analyzed its expression in relation to MYCN and E2F-1 expression in a separate cohort (n=117) using QPCR. Most importantly, high Skp2 expression proved to be a highly significant marker of dire prognosis independent of both MYCN status and disease stage, on the basis of multivariate analysis of event-free survival (hazard ratio, 3.54
2007-06-01 | E-CVDE-3 | biostudies-arrayexpress
Project description:Neuroblastoma (NB) with MYCN amplification is a highly metastatic tumor in children, and unraveling the key players involved in MYCN-induced invasion may identify new targets for therapy. Epithelial-mesenchymal transition (EMT) plays a critical role in promoting metastasis and we have recently determined that MYCN interacts with LSD1, a histone de-methylase flavin oxidase, which has been found to promote EMT. We show here that LSD1 affects motility and invasiveness of NB cells through transcription modulation of the metastasis suppressor NDRG1, N-Myc Downstream-Regulated Gene 1. LSD1 co-localizes with MYCN at the promoter region of the NDRG1 gene and it inhibits its expression. LSD1-inhibition relieves NDRG1 repression induced by MYCN with concomitant block of motility and invasiveness of NB cells, and such effects were recapitulated by overexpressing NDRG1. Moreover, we found that low NRDG1 and high LSD1 levels in NB patients were associated with poor survival. These data suggest that LSD1 inhibition may knock down the ability of MYCN-amplified Neuroblastomas to metastasize. Our findings elucidate a mechanism of how MYCN/LSD1 control motility and invasiveness of NB cells through transcription regulation of NDRG1 expression and they suggest that pharmacological targeting of LSD1 could inhibit the NB metastatic process.
2016-12-31 | GSE80753 | GEO
Project description:To identify the MYCN transcription factor binding sites across the genome, we performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) using anti-MYCN and anti-IgG antibodies on a MYCN-amplified NB cell line, SK-N-BE(2)-C.
2016-05-16 | GSE72640 | GEO