Expression profiling of murine neuroblastoma in transgenic mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE32386 | GEO | 2012/04/01
SECONDARY ACCESSION(S): PRJNA147967
REPOSITORIES: GEO
Similar Datasets
Project description:Neuroblastoma is an embryonal tumor arising from the neural crest. It can be mimicked in mice by neural crest-specific overepxression of oncogenes such as MYCN or mutated ALK. Expression profiling of murine neuroblastoma driven by MYCN were compared to those driven by mutated ALK and to mouse normal adrenal tissue.
2012-03-31 | E-GEOD-32386 | biostudies-arrayexpress
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.
2012-07-05 | GSE35560 | GEO
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:Neuroblastoma is an embryonal neoplasm that remains of dramatic prognosis in its aggressive forms. Activating mutations of the ALK tyrosine kinase receptor have been identified in sporadic and familial cases of this cancer. We generated knock-in mice carrying the two most frequent Alk mutations observed in neuroblastoma patients. We used microarrays to detail the global programme of gene expression underlying the impact of ALK mutations on neuroblastoma formation in a MYCN amplified background. We selected several murine neuroblastoma tumors for RNA extraction and hybridization on Affymetrix microarrays. We generated three groups of tumors: 10 MYCN amplified tumors, 11 MYCN amplified/ALK F1174L tumors and 10 MYCN amplified/ALK R1275Q tumors.
2014-06-24 | E-GEOD-46583 | biostudies-arrayexpress
Project description:Neuroblastoma is a neural crest-derived embryonal tumor or the postganglionic sympathetic nervous system. Neuroblastomas show heterogeneous biologic and clinical features and , whereas a subset may undergo spontaneous differentiation or regression with little or no therapy, the majorities are difficult to cure with current modalities. The origin of these tumours remains unknown in most cases, although a number of familial cases have been associated with mutations of the ALK gene. In this study we established both phosphoproteomic and gene expression profiles of ALK activity in neuroblastoma cells exposed to first and third generation ALK TKIs, to identify the underlying molecular mechanisms and identify relevant biomarkers, signaling networks, and new therapeutic targets.
2018-11-27 | PXD011187 | Pride
Project description:Circular RNAs (circRNAs), a noncoding RNA class originating from alternative splicing, are highly abundant in neural tissues and were shown to regulate gene expression e.g. by interacting with microRNAs and RNA-binding proteins. Neuroblastoma is an embryonal neoplasia, which arises from undifferentiated neural crest cells. Here, we aimed to explore, whether circRNAs influence the pathogenesis of high-risk neuroblastoma. We performed whole-transcriptome sequencing of 104 primary neuroblastoma samples of all risk-groups and identified 5,203 unique circRNAs involving 2,302 genes. Candidate circRNA expression did not correlate with host gene expression, indicating independent regulatory mechanisms. circRNAs were significantly downregulated in the MYCN-amplified high-risk tumors. These findings were independently reproduced in a tetracycline-inducible MYCN-overexpression system based on a non MYCN-amplified neuroblastoma cell line, suggesting that MYCN drives this global circRNA repression. We identified the RNA helicase DHX9 as a mediator of this global suppressive effect of MYCN on circRNAs. Comparing our RNA sequencing data with other cancers and controls revealed a circRNA subset specifically upregulated in neuroblastoma that included a circRNA derived from the ARID1A tumor suppressor gene. Specific circARID1A knockdown resulted in reduced proliferation, cell numbers and viability, prompted apoptosis and induced a differentiated phenotype. Neither knockdown, nor overexpression of circARID1A influenced ARID1A mRNA and protein levels significantly. To dissect the potential mode of function, we performed a pulldown assay with subsequent mass spectrometry. We identified the RNA-binding protein KHSRP as an interaction partner that participates in the mechanism of action of circARID1A. In summary, this study highlights an important role of circRNAs in neuroblastoma biology and may establish this RNA class as a future therapeutic target and biomarker.
2023-04-06 | PXD026053 | Pride
Project description:Neuroblastoma is an embryonal neoplasm that remains of dramatic prognosis in its aggressive forms. Activating mutations of the ALK tyrosine kinase receptor have been identified in sporadic and familial cases of this cancer. We generated knock-in mice carrying the two most frequent Alk mutations observed in neuroblastoma patients. We used microarrays to detail the global programme of gene expression underlying the impact of ALK mutations on neuroblastoma formation in a MYCN amplified background.
2014-06-24 | GSE46583 | GEO
Project description:Neuroblastoma is a common childhood malignant tumor of neural crest origin with remarkable heterogeneity in outcomes. Amplification of the oncogene MYCN is strongly associated with highly malignant behaviour and poor prognosis. Here, we used human ESC-derived neural crest model to recapitulate the initiation of MYCN-driven neuroblastoma and to identify MYCN downstream effectors. Our results show that induced deregulation of MYCN in human neural crest progenitor cells is sufficient to induce tumors that recapitulate the pathological and molecular features of human MYCN-amplified neuroblastoma(MNA-NB). By using this platform, we are able to identify a group of 28 genes that are associated with MYCN expression level only in MNA-NB.
2021-09-01 | GSE137975 | GEO
Project description:Neuroblastoma (NB) is an embryonic tumor arising from immature sympathetic nervous system progenitor cells. MYCN and ALK are driver oncogenes both of which are specifically expressed during early neurogenesis. This is in line with the assumption that NB arises through disruption of normal developmental processes. MYCN has a broad impact on the tumor phenotype; however, the details of the MYCN driven oncogenic program are far from clear. In recent studies we demonstrated that MYCN drives the expression of a defined set of miRNAs that tightly control the expression of several key MYCN target genes, including several components of the TGFβ signaling pathway. In order to gain further insight into the role of miRNAs in NB initiation and progression, we evaluated miRNA profiles of hyperplastic ganglia and tumors isolated from MYCN transgenic mice.
2014-10-01 | E-MTAB-2618 | biostudies-arrayexpress
Project description:Neuroblastoma is an embryonic tumor arising from immature sympathetic nervous system progenitor cells. MYCN and ALK are driver oncogenes both of which are specifically expressed during early neurogenesis. This is in line with the assumption that neuroblastoma arises through disruption of normal developmental processes. MYCN has a broad impact on the tumor phenotype; however, the details of the MYCN driven oncogenic program are far from clear. In order to gain further insight into the role of gene expression during neuroblastoma initiation and progression, we evaluated gene expression profiles of hyperplastic ganglia and tumors isolated from MYCN transgenic mice.
2016-02-28 | E-MTAB-3247 | biostudies-arrayexpress