Transcriptomics,Multiomics

Dataset Information

3

TH-MYCN Mice with Caspase-8 Deficiency Develop Advanced Neuroblastoma with Bone Marrow Metastasis


ABSTRACT: 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

OTHER RELATED OMICS DATASETS IN: PRJNA182245PRJNA179446

ORGANISM(S): Mus musculus  

SUBMITTER: Jill M Lahti   William A Weiss  Chrisopher Calabrese  Tal Teitz  David Finkelstein  Madoka Inoue  Razqallah Hakem  Jerold E Rehg  Wei Zhao  Marcus B Valentine  Melisa D Johnson  Yong-Dong Wang  Marcelo Rubinstein  Kejin Zhu 

PROVIDER: E-GEOD-42254 | ArrayExpress | 2013-05-22

SECONDARY ACCESSION(S): GSE42254PRJNA179446

REPOSITORIES: GEO, ArrayExpress

Dataset's files

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E-GEOD-42254.idf.txt Idf
E-GEOD-42254.processed.1.zip Processed
E-GEOD-42254.raw.1.zip Raw
E-GEOD-42254.sdrf.txt Txt
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Publications


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 used transgenic model, the Th-MYCN mouse, exhibits limited metastasis to this site. Here, we establish the first  ...[more]

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