Transcriptome profiling of caspase-2 deficient lymphomas from EμMyc and neuroblastomas from Th-MycN mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA510620 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The project used next generation sequencing for RNA-seq analysis, to identify transcriptome changes associated with tumorigenesis in two different caspase-2 knockout mice models. We describe key changes in both lymphoma and neuroblastoma associated genes in the two tumor types that may contribute to tumor outcome following loss of Casp2. We identified a panel of genes with altered expression in Th-MYCN/Casp2-/- tumors, that are strongly associated with neuroblastoma outcome, and which have roles in melanogenesis, Wnt and Hippo pathway signaling, that also contribute to neuronal differentiation. In addition, we found that key changes in gene expression in the EμMyc/Casp2-/- tumors, are associated with increased immune signaling and suggest that Casp2 deficiency augments immune signaling pathways that may be in turn, enhance lymphomagenesis. Overall, our study has identified new genes and pathways that contribute to the caspase-2 tumor suppressor function and highlight distinct roles for caspase-2 in different tissues.
2019-01-28 | GSE124051 | GEO
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
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 13 NB tumors in wt and transgenic mice
2013-05-22 | E-GEOD-42254 | biostudies-arrayexpress
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.
2013-05-22 | GSE42254 | GEO
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.
2013-05-22 | GSE42548 | GEO
Project description:Neuroblastoma is the most common extra-cranial malignancy in childhood and accounts for approximately 15% of childhood cancer deaths. Amplification of N-Myc in neuroblastoma is associated with aggressive disease and predicts for poor prognosis. Novel therapeutic approaches are therefore essential to improving patient outcomes in this setting. The histone deacetylases are known to interact with N-Myc and regulate numerous cellular processes, including differentiation in neuroblastoma. We therefore investigated the antitumor activity of the histone deacetylase inhibitor, panobinostat in the setting of N-Myc amplified neuroblastoma using the TH-MYCN murine model. Continuous treatment of tumor bearing TH-MYCN transgenic mice with panobinostat for 9 weeks led to a significant improvement in survival as compared to mice treated with vehicle, or continuous treatment with panobinostat for a three week period. Panobinostat induced rapid tumor regression with no regrowth observed during the treatment period. Tumor response was associated with an initial apoptosis phenotype mediated via up-regulation of BMF and BIM. When treated was stopped at three weeks 100% of mice relapsed with aggressive neuroblastoma. Differentiation of neuroblastoma into benign ganglioneuroma, with a characteristic increase in S100 expression and reduction of N-Myc expression, was observed in mice treated for nine weeks, resulting in a sustained remission on 90% of mice treated. RNA-sequencing analysis of tumors from treated animals confirmed significant up-regulation of gene pathways associated with apoptosis and differentiation as early as 24 hours after treatment. Together our data demonstrate the potential of panobinostat as a therapeutic strategy for high-risk neuroblastoma patients. Eight homozygous TH-MYCN mice bearing neuroblastomas were treated with either 5mg/kg panobinostat (4 animals) or vehicle (4 animals) for 24hr (two doses) and tumours harvested 4hr post the second dose.
2015-07-15 | E-GEOD-69869 | biostudies-arrayexpress
Project description:Amplification of MYCN is the most prominent genetic marker of high-stage neuroblastoma, a childhood tumor originating from the neural crest. We generated a transgenic mouse with Cre-conditional induction of MYCN in dopamine beta hydroxylase expressing cells that develops murine neuroblastomas.
2014-09-01 | GSE51297 | GEO
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
Project description:Amplification of MYCN is the most prominent genetic marker of high-stage neuroblastoma, a childhood tumor originating from the neural crest. We generated a transgenic mouse with Cre-conditional induction of MYCN in dopamine beta hydroxylase expressing cells that develops murine neuroblastomas. The expression profiles of six tumors from adrenals and two tumors from superial cervical gangliae were compared to three non-malignant adrenals from wildtype mice. These profiles of adrenals have been previously described (Molenaar et al., Nature Genetics 2012). Wild type samples are accessible at the AMC webpage: http://hgserver1.amc.nl/cgi-bin/r2/main.cgi, and accessible for registered users.
2014-09-01 | E-GEOD-51297 | biostudies-arrayexpress
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