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Series GSE94914 Query DataSets for GSE94914
Status Public on Sep 25, 2017
Title MYCN induces neuroblastoma in primary neural crest cells
Organism Mus musculus
Experiment type Expression profiling by array
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.
 
Overall design 8 neural crest cell derived N-myc amplified p53 mixed neuroblastoma mouse tumors
 
Contributor(s) Olsen RR, Otero JH, Garcia-Lopez J, Wallace K, Finkelstein D, Rehg JE, Yin Z, Wang M, Freeman KW
Citation(s) 28459463
Submission date Feb 15, 2017
Last update date Feb 21, 2018
Contact name David Finkelstein
E-mail(s) david.finkelstein@stjude.org
Phone 9014953931
Organization name St Jude Children's Research Hospital
Department Computational Biology
Street address 332 N. Lauderdale St.
City Memphis
State/province TN
ZIP/Postal code 38105
Country USA
 
Platforms (1)
GPL16570 [MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version]
Samples (8)
GSM2491823 Tum001
GSM2491824 Tum002
GSM2491825 Tum003
Relations
BioProject PRJNA374805

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Series Matrix File(s) TXTHelp

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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