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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 25, 2017 |
| Title |
MYCN induces neuroblastoma in primary neural crest cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
8 neural crest cell derived N-myc amplified p53 mixed neuroblastoma mouse tumors
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| Contributor(s) |
Olsen RR, Otero JH, Garcia-Lopez J, Wallace K, Finkelstein D, Rehg JE, Yin Z, Wang M, Freeman KW |
| Citation(s) |
28459463 |
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| Submission date |
Feb 15, 2017 |
| Last update date |
Feb 21, 2018 |
| Contact name |
David Finkelstein |
| E-mail(s) |
david.finkelstein@stjude.org
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| Phone |
9014953931
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| Organization name |
St Jude Children's Research Hospital
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| Department |
Computational Biology
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| Street address |
332 N. Lauderdale St.
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| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA374805 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE94914_RAW.tar |
73.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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