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Transcriptomic changes in MYC and PRC2 targets are prominent events in the early pathogenesis of neuroblastoma in TH-MYCN mice

ABSTRACT: It has been already reported that there are undifferentiated/proliferating neuroblasts in the postnatal sympathetic ganglia in TH-MYCN mice. We established suitable spheroid culture condition that selectively isolates undifferentiated neuroblasts from superior mesenteric ganligon (SMG) of TH-MYCN mice. In the present study, in order to investigate the transcriptomic differences between embryonic day 13.5 (E13.5) WT derived primary spheres and E13.5 TH-MYCN derived passageable spheres, we carried out microarray gene expression analysis. We investigated critical molecular events in MYCN-transformed neuroblastoma cells in TH-MYCN mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE87783 | GEO | 2017/04/01

SECONDARY ACCESSION(S): PRJNA347591

REPOSITORIES: GEO

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MYCN-transformed neuroblasts from TH-MYCN mice are selectively isolated and maintained as spheres in vitro

Project description:It has been already reported that there are undifferentiated/proliferating neuroblasts in the postnatal sympathetic ganglia in TH-MYCN mice. We established suitable spheroid culture condition that selectively isolates undifferentiated neuroblasts from superior mesenteric ganligon (SMG) of TH-MYCN mice. In the present study, in order to investigate the transcriptomic differences among 3-week-old WT SMG, TH-MYCN (hemizygote) SMG, and TH-MYCN (hemizygote) spheres, we carried out microarray gene expression analysis. We investigated whether or not undifferentiated cells observed in TH-MYCN SMG were selectively isolated and maintaned as spheres.

2017-04-01 | GSE87782 | GEO

Array comparative genomic hybridization of spheres derived from TH-MYCN (hemizygote) mice [Agilent-027441]

Project description:It has been already reported that there are undifferentiated/proliferating neuroblasts in the postnatal sympathetic ganglia in TH-MYCN mice, a neuroblastoma model. We established suitable spheroid culture condition that selectively isolates undifferentiated neuroblasts from superior mesenteric ganligon (SMG) of TH-MYCN mice. In order to investigate the chromosomal alterations (gains or losses) of spheres derived from TH-MYCN mice, we carried out array comparative genomic hybridization. We investigated whether chromosomal alterations occured during early neuroblastoma tumorigenesis in TH-MYCN mice.

2017-04-01 | GSE89740 | GEO

Retinoic acid-free spheroid culture condition is suitable for growth of TH-MYCN neuroblasts

Project description:It has been already reported that there are undifferentiated/proliferating neuroblasts in the postnatal sympathetic ganglia in TH-MYCN mice. Given the fact that neuroblastoma is derived from sympathoadrenal progenitors which are originated from neural crest stem cells, we attempted to use the well-established culture condition that has been utilized to maintain derivatives of neural crest stem cells. However, the medium contained retinoic acid (RA) which is known to induce neuroblastoma differentiation and is used in clinical treatment against high-risk patients. In the present study, the medium with RA (RA (+) medium) and without RA (RA (-) medium) were compared. Since undifferentiated neuroblasts are observable at one of the sympathetic ganglia, superior mesenteric ganglion (SMG), in 3-week-old TH-MYCN hemizygote (TH-MYCN+/-) mice with 129+Ter/SvJcl mice background, we dissected and dissociated the SMG to prepare single cells. These cells were cultured in either RA (+) or RA (-) media. Spheres formed in either RA (+) or RA (-) medium were subjected to microarray analysis.

2017-04-01 | GSE87781 | GEO

Mus musculus

Project description:MYCN-transformed neuroblasts from TH-MYCN mice are selectively isolated and maintained as spheres in vitro

| PRJNA347592 | ENA

Array comparative genomic hybridization of tumor tissue developed in TH-MYCN (hemizygote) mice [Agilent-015028]

Project description:In order to investigate the chromosomal alterations (gains or losses) of tumor tissuees developed in TH-MYCN mice, a neuroblastoma model, we carried out array comparative genomic hybridization. We investigated whether chromosomal alterations occured in the tumor tissues developed in the abdomen of TH-MYCN hemizygote mice.

2017-04-01 | GSE89739 | GEO

Expression data from neuroblastoma of TH-MYCN/KI RetM919T mice

Project description:The RET gene has been identified previously as a target of activated ALK at the mRNA level in both human neuroblastoma cell lines and primary tumors as well as in murine tumors driven by mutated Alk and MYCN. Moreover, it has been shown that tumor growth of murine TH-MYCN/KI Alkmut tumors was impaired upon Ret inhibition by the vandetanib inhibitor, suggesting RET as a therapeutic target in ALK mutated neuroblastoma. To further demonstrate the crucial role of RET in ALK mutated driven neuroblastoma oncogenesis, transgenic TH-MYCN mice were bred with KI RetM919T tumors. We document an oncogenic cooperation between activated Ret and MYCN overexpression in neuroblastoma formation. We used microarrays to analyze the global programme of gene expression of MYCN/RetM919T tumors and compare these profiles with profiles of MYCN/Alkmut tumors (GSE46583). Altogether, our data show that MYCN/RetM919T tumors present with expression profiles close to MYCN/Alkmut tumors.

2017-09-15 | GSE72678 | GEO

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

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 24 NB tumors and 5 bone marrow samples in wt and transgenic mice.

2013-05-22 | E-GEOD-42548 | biostudies-arrayexpress

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

2013-05-22 | E-GEOD-42254 | biostudies-arrayexpress

RNA-seq of TH-MYCN driven neuroblastoma mice +/- ALK F1178S mutation and +/- ALKAL2 overexpression

Project description:ALK is a tyrosine kinase receptor and oncogene in neuroblastoma (NB). The receptor is activated by the ALKAL2 ligand, but it is unknown whether missregulation of this ligand may play a role in NB carcinogenesis. Here, a TH-MYCN driven neuroblastoma mice was created +/- ALK F1178S mutation and +/- ALKAL2 overexpression

2020-11-24 | E-MTAB-9600 | biostudies-arrayexpress

Expression profiling of transgenic TH-MYCN mice with palpable tumors treated with MLN8054 or vehicle

Project description:Transgenic TH-MYCN mice with palpable tumors (40-80 days old) treated with 40mg/kg MLN8054 or vehicle. MLN8054 was administered via oral gavage. Animals were sacrificed when pathologic signs of tumor burden (predominantly poor mobility) were apparent. Animals were treated in accordance with national animal welfare guidelines. Mice were allowed access to food and water ad libitum.

2013-07-01 | E-MTAB-1118 | biostudies-arrayexpress

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